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![Subdivisions of the Autonomic Nervous System
Sympathetic Parasympathetic
Primary
Neurotransmitter
norepinephrine
epinephrine (~20%)
acetylcholine
Receptors
&
Second
Messenger
Systems
Adrenergic GPCRs
α1 – IP3/DAG, ↑[Ca2+
]i ↑PKC
α2 - ↓cAMP/PKA
β1 - ↑cAMP/PKA
β2 - ↑cAMP/PKA
β3 - ↑cAMP/PKA
Muscarinic GPCRs
M1 – IP3/DAG, ↑[Ca2+
]i ↑PKC
M2 – ↓cAMP/PKA, ↑PI(3)K
M3 – ↓cAMP/PKA,
IP3/DAG, ↑[Ca2+
]i ↑PKC
M4 –
M5 – IP3/DAG, ↑[Ca2+
]i ↑PKC
Adrenal Medulla
(epi:norepi::80:20)](https://image.slidesharecdn.com/anscns-160607205009/75/ANS-SYMPATHETIC-and-PARASYMPATHETIC-107-2048.jpg)
![OH OP
[2]
degradation
to VMA
insulin activation of protein
phosphatase to dephosphorylate
enzymes[7]
α
[5]
γ
β
GTPase
αGDP
epinephrine
phosphorylation
of β-receptor by
β-ARK decreases
activity even with
bound hormone
OH OH
[3]
OP OP
[4]
OPOP
binding of β-arrestin
further inactivates
receptor despite
bound hormone
AC
cAMPATP
activated PKA
phosphorylates
enzymes
[6]
AMP
phosphodiesterase
GTP
[1]
dissociation
Figure 6. Mechanisms for terminating the signal generated by epinephrine
binding to a β-adrenergic receptor](https://image.slidesharecdn.com/anscns-160607205009/75/ANS-SYMPATHETIC-and-PARASYMPATHETIC-123-2048.jpg)
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ANS (SYMPATHETIC and PARASYMPATHETIC)
- 1. Nervous System (General outlineof central nervous system and autonomic nervous system) Supriya Mana
- 2. Composition of NervousSystem • Two main divisions – 1) Central Nervous system (CNS) brain and spinal chord – 2)Peripheral Nervous System (PNS) nerves
- 3. Remember from Homeostasis •Message is received from sensory receptor along sensory neuron (afferent pathway) • Messages reaches brain and is integrated (control center) • Reaction command sent down efferent pathway along motor neuron (motor output)
- 4. Types of MotorActions • Somatic – Happens in skeletal muscle – voluntary • Autonomic – Happens in smooth and cardiac muscle – Involuntary – 2 parts • Sympathetic and parasympathetic
- 5. Cells of theNervous System • Broken down into two groups – 1) supporting cells – 2) neurons
- 6. Examples of Neuroglia(supporting cells) • Astrocytes – anchor neurons to capillaries • Microglia – phagocytes (digest debris and dead cells) • Ependymal cells- ciliated; always on surface near spinal fluid; circulates fluid
- 7. One more Neuroglialcell (in CNS) • Oligodendrocytes – fatty; insulated nerve fibers • Produce myelin sheath which surround and insulate the nerve fiber
- 8. In PNS • Insteadof oligodendrocytes, they have Schwann cells, which insulate the nerve fiber • Satellite cells – form protective layer around nerve cell body
- 9. Neurons • Specifically designedto transmit message (nerve impulse)
- 10. Parts of aNeuron • 1)Cell Body- contains nucleus • 2) fiber (process)- carries message to next neuron – Toward cell body = dendrites – Away from cell body = axon
- 11. Axonal Terminal • Asan axon ends, it branches into hundreds of synapses. • Releases neurotransmitters to next neuron or muscle
- 12. Myelination of Neurons •In CNS, the fatty covering is oligodendrocyte • In PNS, fatty myelin forms Schwann cells, which increase transmission rate. • Gaps between Schwann cells= Nodes of Ranvier
- 13. INTRODUCTION • Much ofthe action of the body in maintaining such as cardiovascular, gastrointestinal and thermal homeostasis occurs through the autonomic nervous system (ANS). • The ANS is our primary defense against challenges, to maintain homeostasis. It provides involuntary control and organization of both maintenance and stress responses. 13
- 14. FUNCTIONAL ANATOMY Nervous System CentralNervous System Peripheral Nervous System Somatic Autonomic Sympathetic Parasympathetic Enteric Nervous System 14
- 15. DIFFeReNCe beTweeNSomatic Autonomic Organ suppliedSkeletal muscles All other organs Distal most synapse Within CNS Outside the CNS(i.e. ganglia) Nerve fibers Myelinated Preganglionic - myelinated Postganglionic- nonmyelinated Peripheral plexus formation Absent Present Efferent transmitter ACH ACH, Nor-adrenaline Effect of nerve section on organ supplied Paralysis and Atrophy Activity maintained, no Atrophy 15
- 16.
- 17. Comparison of Autonomicand Somatic Motor Systems • Autonomic nervous system – Chain of two motor neurons • Preganglionic neuron • Postganglionic neuron – Conduction is slower due to thinly or unmyelinated axons Pre-ganglionic Ganglion Post-ganglionic
- 18. Autonomic Nervous System •Often work in opposition • Cooperate to fine- tune homeostasis • Regulated by the brain; hypothalamus, pons and medulla • Can also be regulated by spinal reflexes; no higher order input • Pathways both consist of a two neuron system Preganglionic neuron autonomic ganglion postganglionic neuron target from CNS outside CNS
- 19. Fig. 45.34(TE Art)Hypothalamusactivates sympathetic division of nervous system Heart rate, blood pressure, and respiration increase Blood flow to skeletal muscles increases Stomach contractions are inhibited Adrenal medulla secretes epinephrine and norepinephrine
- 21. Sympathetic Fight or Flight,Dealing with stress, thoracolumber, intermediolateral column, T1 -L2 Parasympathetic Rest and Digest, Vegging Craniosacral S2-S4,
- 22. Sympathetic nerve endingsalso activate the release of NE and E from the adrenal medulla Enhances effects of NE from sympathetic nerve endings
- 23. The Autonomic SystemTheAutonomic System
- 24. Sympathetic • Sometimes calledthe “thoracolumbar” division • Short preganglionic neurons; long postganglionic neurons; ganglia are called the chain ganglia • Preganglionic neurons secrete Ach onto nicotinic receptors • Postganglionic neurons secrete NE on to α or β receptors • Target tissues are smooth muscle, cardiac muscle, endocrine glands, brown fat
- 25. Parasympathetic •Sometimes called the “cranio-sacraldivision •Long preganglionic neurons; •short postganglionic neurons (often in the target organ) •Preganglionic neurons secrete Ach on to nicotinic receptors •Postganglionic neurons secrete Ach on to muscarinic receptors •Target tissues are smooth muscle, cardiac muscle, exocrine glands, brown fat
- 26. Anatomical Differences inSympathetic and Parasympathetic Divisions
- 27. Anatomical Differences inSympathetic and Parasympathetic Divisions
- 28. Similarities between Sympathetic& ParasympatheticSimilarities between Sympathetic & Parasympathetic • Both are efferent (motor) systems: “visceromotor” • Both involve regulation of the “internal” environment generally outside of our conscious control: “autonomous” • Both involve 2 neurons that synapse in a peripheral ganglion and Innervate glands, smooth muscle, cardiac muscle CNS ganglion preganglionic neuron postganglionic neuron glands smooth muscle cardiac muscle
- 29. Differences between Sympathetic& ParasympatheticDifferences between Sympathetic & Parasympathetic Location of Preganglionic Cell Bodies Thoracolumbar T1 – L2/L3 levels of the spinal cord Craniosacral Brain: CN III, VII, IX, X Spinal cord: S2 – S4 Sympathetic Parasympathetic
- 30. Sympathetic CNS ganglion short preganglionic neuron longpostganglionic neuron target Parasympathetic CNS ganglion long preganglionic neuron target short postganglionic neuron Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic Relative Lengths of Neurons
- 31. Parasympathetic Overview of theAutonomic Nervous SystemOverview of the Autonomic Nervous System Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic Neurotransmitters ACh, + NE (ACh at sweat glands), + / -, α & ß receptors ACh, + / - muscarinic receptors • All preganglionics release acetylcholine (ACh) & are excitatory (+) • Symp. postgangl. — norepinephrine (NE) & are excitatory (+) or inhibitory (-) • Parasymp. postgangl. — ACh & are excitatory (+) or inhibitory (-) Sympathetic • Excitation or inhibition is a receptor-dependent & receptor-mediated response ACh, +
- 32. Overview of theAutonomic Nervous SystemOverview of the Autonomic Nervous System Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic Target Tissues ParasympatheticSympathetic • Organs of head, neck, trunk, & external genitalia • Organs of head, neck, trunk, & external genitalia • Adrenal medulla • Sweat glands in skin • Arrector muscles of hair • ALL vascular smooth muscle » Sympathetic system is distributed to essentially all tissues (because of vascular smooth muscle) » Parasympathetic system never reaches limbs or body wall (except for external genitalia)
- 33. Overview of ANSOverviewof ANS Functional Differences Sympathetic • “Fight or flight” • Catabolic (expend energy) Parasympathetic • “Feed & breed”, “rest & digest” • Homeostasis » Dual innervation of many organs — having a brake and an accelerator provides more control
- 35. The reflex arc Theautonomic reflex arc The somatic reflex arc Origin Lateral horn cells Anterior horn cells Efferent Relay in autonomic ganglia outside the CNS. Supply the effector organ directly. Inter neuron ------------------------ present Effector organs Smooth , cardiac muscles skeletal
- 37.
- 38. Fig. 45.32(TE Art) Viscera Autonomic ganglion Postganglionicneuron Autonomic motor reflex Interneuron Dorsal root ganglion Preganglionic neuron Sensory neuron Spinal cord
- 39. Autonomic and SomaticMotor Systems
- 40. Structure of spinalnerves: Somatic pathwaysStructure of spinal nerves: Somatic pathways dorsal root dorsal root ganglion ventral root spinal nerve dorsal ramus ventral ramus dorsal horn ventral horn somaticsomatic sensorysensory nervenerve (GSA)(GSA) somaticsomatic motormotor nervenerve (GSE)(GSE) CNS inter- neuron Mixed SpinalMixed Spinal NerveNerve Mixed SpinalMixed Spinal NerveNerve gray ramus communicans white ramus communicans sympathetic ganglion
- 41. spinal nerve dorsal ramus ventral ramus gray ramus communicans whiteramus communicans sympathetic ganglion intermediolateral gray column Structure of spinal nerves: Sympathetic pathwaysStructure of spinal nerves: Sympathetic pathways
- 42. Sympathetic Division ofthe ANS
- 43. somatic tissues (body wall,limbs) visceral tissues (organs) Sympathetic System: Preganglionic Cell BodiesSympathetic System: Preganglionic Cell Bodies • Preganglionic cell bodies in intermediolateral gray • T1 — L2/L3 • Somatotopic organization intermediolateral gray columns lateral horn T1 – L2/L3 Clinical Relevance » dysfunction due to cord injury » spinal nerve impingement & OMM » referred pain
- 44. Sympathetic System: PostganglionicCell BodiesSympathetic System: Postganglionic Cell Bodies Paravertebral ganglia Prevertebral ganglia • celiac ganglion • sup. mesent. g. • inf. mesent. g. aorta sympathetic trunk (chain) 1. Paravertebral ganglia • Located along sides of vertebrae • United by preganglionics into Sympathetic Trunk • Preganglionic neurons are thoracolumbar (T1–L2/L3) but postganglionic neurons are cervical to coccyx • Some preganglionics ascend or descend in trunk synapse at same level ascend to synapse at higher level descend to synapse at lower level
- 45. Sympathetic System: PostganglionicCell BodiesSympathetic System: Postganglionic Cell Bodies Paravertebral ganglia Prevertebral ganglia • celiac ganglion • sup. mesent. g. • inf. mesent. g. aorta sympathetic trunk (chain) 2. Prevertebral (preaortic) ganglia • Located anterior to abdominal aorta, in plexuses surrounding its major branches • Preganglionics reach prevertebral ganglia via abdominopelvic splanchnic nerves abdominopelvic splanchnic nerve
- 46.
- 47. Sympathetic System: SummarySympatheticSystem: Summary T1 L2 4- somatic tissues (body wall, limbs) visceral tissues (organs) postganglionics via 31 spinal nerves to somatic tissues of neck, body wall, and limbs sympathetic trunk prevertebral ganglia 2- Cardiopulmonary Splanchnics: postganglionic fibers to thoracic viscera 3- Abdominopelvic Splanchnics: preganglionic fibers to prevertebral ganglia, postganglionic fibers to abdominopelvic viscera 1- Cervical division
- 48. 1- Cervical division Origin:T1-2 Course: preganglionic fibres reach the sympathetic chain and then ascend upwards to relay in the superior cervical ganglion. Postganglionic neuron: pass from ganglion to the following organs:- • EYE: pupil dilatation, widening of palpebral fissure, exophthalmos, Vasoconstriction of eye b.v. and Relaxation of ciliary muscle. • Salivary gland : trophic secretion, Vasoconstriction of its blood vessels and Squeezing of salivary secretion. • Lacrimal gland: Trophic secretion and Vasoconstriction. • Face skin blood vessel: Vasoconstriction of (Pale color). • Sweet secretion: copious secretion. • Hair: erection due to contraction of erector pilae muscles.. • Cerebral vessels: Weak vasoconstriction
- 49. Sympathetic Pathways tothe Head
- 50. (2) Cardiopulmonary division Origin:Lateral horn cells of upper 4-5 thoracic segments. Course: Preganglionic neurons reach the sympathetic chain to relay in the three cervical ganglion and upper four thoracic ganglion. The postganglionic arise from these ganglia supply the following structures:- • Heart: Increase all properties of cardiac muscle (contraction, rhythmicity, excitability, conductivity. • Coronary vessels, its sympathetic supply. At first it causes vasoconstriction, and then it causes vasodilatation due to accumulation of metabolites. • Bronchi: Broncho dilation, decrease bronchial secretions and vasoconstriction of pulmonary blood vessels.
- 51. Sympathetic Pathways toThoracic Organs
- 52. 3- Splanchnic division Origin:lateral horn cells of the lower six thoracic and upper four lumber segments. Course: Preganglionic neurons originate from these segments reach the sympathetic chain where they pass without relay, and then they divided into two branches: (1) Greater splanchnic nerve (2) Lesser splanchnic nerve. Greater splanchnic nerve: • Origin: Preganglionic nerves fibers emerge from lateral horn cells of lower six thoracic segments and then relay in the collateral ganglion in the abdomen. • Course: Postganglionic nerve fibers arise from these ganglia (celiac, superior mesenteric and inferior mesenteric ganglia) and supply the abdominal organs causing the following effects: • Vasoconstriction: of most arteries of stomach, small intestine, proximal part of large intestine, kidney, pancreas and liver. • Relaxation of the musculature of: stomach, small intestine and proximal part of large intestine. • Contraction of sphincters: of the stomach and intestine leading to (food retention). • Contraction of the capsule: of the spleen leading to evacuation of about 200 ml of blood. • Breakdown of the glucose in the liver: (glycogenolysis) leading to increase of blood glucose level. • Stimulation of adrenal medulla: Secrete adrenaline and noradrenalin.
- 53. Sympathetic Pathways tothe Abdominal Organs
- 56. Lesser splanchnic nerve Origin:Preganglionic nerve fibers originate from the lateral horn cells of the 12 thoracic and upper two lumber segments. Course: 2 nerves from both sides unite together forming the presacral nerve, which proceeds to pelvis and divided into two branches (hypogastric nerves), then relay in the inferior mesenteric ganglion. Postganglionic nerve fiber supplies the following pelvic viscera: Urinary bladder: Relaxation of its wall. – Contraction of internal urethral sphincter. – Leading to urine retention. Rectum: – Relaxation of the distal part of large intestine. – Relaxation of the rectum wall. – Contraction of the internal anal sphincter. – Leading to feces retention.
- 57. Genital organs: - Vasoconstrictionof its blood vessels. –Leading to shrinkage of penis and clitoris. Vas deferens: - Contraction of its wall, and wall of seminal vesicles, ejaculatory ducts and prostate - Leading to ejaculation.
- 58. Sympathetic Pathways tothe Pelvic Organs
- 59. (4) Somatic division Origin:Preganglionic nerve fibers arise from all lateral horn cells of all sympathetic segments, and then relay in the cervical and sympathetic chain ganglia. Course: Postganglionic nerve fibers emerge from these ganglia proceeds outside the central nervous system to return back to spinal cord to join the spinal nerve when it comes out from the anterior horn cells, and supply the following structures: Skin: • Vasoconstriction giving the pale color of the skin. • Stimulation of the sweet glands, the eccrine glands give copious secretion, while the apocrine glands give thick odoriferous secretion. • Hair erection. Skeletal muscle: • Its blood vessels show vasodilatation (V.D.) due to cholinergic effect or vasoconstriction (V.C.) due to a adrenergic effect. • The type of stimulation depends upon the nature of stimulation. • Muscles: its stimulation causing delayed fatigue and early recovery.
- 60. 4- somatic tissues (bodywall, limbs) postganglionics via 31 spinal nerves to somatic tissues of neck, body wall, and limbs sympathetic trunk
- 61. Sympathetic Pathways toPeriphery Figure 15.9
- 62. The Role ofthe Adrenal Medulla in the Sympathetic Division • Major organ of the sympathetic nervous system • Secretes great quantities epinephrine (a little norepinephrine) • Stimulated to secrete by preganglionic sympathetic fibers
- 63.
- 64. ParasympatheticParasympathetic PathwaysPathways Cranial outflow • CNIII, VII, IX, X • Four ganglia in head • Vagus nerve (CN X) is major preganglionic parasymp. supply to thorax & abdomen • Synapse in ganglia within wall of the target organs (e.g., enteric plexus of GI tract) Sacral outflow • S2–S4 via pelvic splanchnics • Hindgut, pelvic viscera, and external genitalia Clinical Relevance » Surgery for colorectal cancer puts pelvic splanchnics at risk » Damage causes bladder & sexual dysfunction
- 65. The Parasympathetic Division •Cranial outflow – Comes from the brain – Innervates organs of the head, neck, thorax, and abdomen • Sacral outflow – Supplies remaining abdominal and pelvic organs
- 66.
- 67. Cranial Nerves • Attachto the brain and pass through foramina of the skull • Numbered from I–XII • Cranial nerves I and II attach to the forebrain – All others attach to the brain stem • Primarily serve head and neck structures – The vagus nerve (X) extends into the abdomen
- 68. The 12 Pairsof Cranial Nerves
- 69. CN I: OlfactoryNerves • Sensory nerves of smell
- 70. CN II: OpticNerve • Sensory nerve of vision
- 71. CN III: OculomotorNerve • Innervates four of the extrinsic eye muscles
- 72. CN IV: TrochlearNerve • Innervates an extrinsic eye muscle
- 73. CN V: TrigeminalNerve • Provides sensory innervation to the face – Motor innervation to chewing muscles
- 74. CN VI: AbducensNerve • Abducts the eyeball
- 75. CN VII: FacialNerve • Innervates muscles of facial expression • Sensory innervation of face • Taste
- 76. CN VIII: VestibulocochlearNerve • Sensory nerve of hearing and balance
- 77. CN IX: GlossopharyngealNerve • Sensory and motor innervation of structures of the tongue and pharynx • Taste
- 78. CN X: VagusNerve • A mixed sensory and motor nerve • Main parasympathetic nerve – “Wanders” into thorax and abdomen
- 79. CN XI: AccessoryNerve • An accessory part of the vagus nerve • Somatic motor function of pharynx, larynx, neck muscles
- 80. CN XII: HypoglossalNerve • Runs inferior to the tongue – Innervates the tongue muscles
- 81. Cranial Outflow • Preganglionicfibers run via: – Oculomotor nerve (III) – Facial nerve (VII) – Glossopharyngeal nerve (IX) – Vagus nerve (X) • Cell bodies located in cranial nerve nuclei in the brain stem
- 82. CN III: OculomotorNerve Origin: Edinger-Westphal nucleus at midbrain. Course: preganglionic from E-W nucleus to rely in the ciliary ganglion. Postganglionic supply: 1- pupillconstrictor muscle 2- ciliary muscle. 3- four of the extrinsic eye muscles. Its stimulation leads to miosis, accommodation to neat vision and movements of the eye ball.
- 83. CN III: OculomotorNerve • Innervates four of the extrinsic eye muscles
- 84. CN VII: FacialNerve Origin: The superior salivary nucleus which is a part of facial nucleus in the lower part of pons. Course: Preganglionic nerve fibers run in the chorda tympani nerve which is a part of facial nerve and relay in:- - Submaxillary ganglion - Sphenopalatine ganglion. • Postganglionic nerve arises from Submaxillary ganglion supply submandibular and sublingual salivary glands and anterior 2/3 of the tongue. • Postganglionic nerve arises from Sphenopalatine ganglion supply the mucosa of the soft palate and nasopharynx and Lacrimal glands. • Its stimulation causes vasodilatation and secretion at their effector organs.
- 85. CN VII: FacialNerve • Innervates muscles of facial expression • Sensory innervation of face • Taste
- 86. CN IX: GlossopharyngealNerve Origin: Glossopharyngeal nerve nucleus in the upper part of the medulla oblongata called inferior salivary nucleus, and then relay in the otic ganglion. Course: Postganglionic nerve fibers arise from otic ganglion supply the parotid salivary gland and posterior 1/3 of the tongue Its stimulation causes vasodilatation and secretion at their effector organs
- 87. CN IX: GlossopharyngealNerve • Sensory and motor innervation of structures of the tongue and pharynx • Taste
- 88. CN X: VagusNerve Origin: Dorsal vagus nucleus in medulla oblongata Course: Postganglionic nerve fibers from the terminal ganglia which supplied from dorsal vagus nucleus and supply the following structures: • HEART: The vagus nerve supplies the both auricles and don't supply the ventricles (and this called vagus escape phenomena). • Its stimulation produces inhibition of all cardiac properties (decrease heart rate, decrease contractility and decrease conductivity). • Its stimulation causes vasoconstriction of coronary vessels and reduction of O2 consumption by cardiac muscle. • These responses lead to bradycardia.
- 89. • Lungs: Vagusstimulation causes: • Bronchoconstriction. • Increased bronchial secretion. • Vasodilatation of pulmonary blood vessels. • These responses lead to precipitation of asthma. Gastrointestinal tract: Vagus stimulation causes: • Contraction of walls of esophagus, stomach, small intestine and proximal part of large intestine. • Relaxation of their corresponding sphincter. • These responses promote deglutition, increased secretion of GIT and evacuation of foods. • Gall bladder: Vagus stimulation causes: • Contraction of the gall bladder wall. • Relaxation of its sphincter. • These responses lead to evacuation of the gall bladder.
- 90. CN X: VagusNerve
- 91. Sacral Outflow Origin: Preganglionicnerve fibers arise from the lateral horn cells of the 2nd, 3rd and 4th sacral segments. Course: These preganglionic passes without relay, then the right and left branches unit together to form the pelvic nerve, the pelvic nerve relay in the terminal ganglia, where the postganglionic nerve fibers emerge and supply the following structures:- Urinary bladder: parasympathetic stimulation causes: - Contraction of the bladder wall - Relaxation of its sphincter. - These responses lead to micturition.
- 92. Rectum and descendingcolon: parasympathetic stimulation causes: - Contraction of its wall. - Relaxation of internal anal sphincter. - These responses lead to defecation. Seminal vesicles and prostate: parasympathetic stimulation -causes: - Secretion of these glands. Erectile tissue: parasympathetic stimulation causes: - Vasodilatation which lead to erection.
- 93. Chemical transmission The travelingof signal in the nervous system between different neurons is mediated by the effect of a chemical substance released at the nerve terminal called chemical transmitter. In the sympathetic nervous system the chemical transmitter is adrenaline, noradrenaline or sometimes acetylcholine. When the chemical transmitter is adrenaline the nerve fiber is called adrenergic, but when the chemical transmitter is acetylcholine, the nerve fiber is called cholinergic.
- 94. Nerves Contact OtherCells at Synapses • The synapse is the relay point where information is conveyed from neuron to neuron by chemical transmitters. • At a synapse the axon usually enlarges to from a button ' which is the information delivering part of the junction. • The terminal button contains tiny spherical structures called synaptic vesicles, each of which can hold several thousand molecules of chemical transmitter. • On the arrival of a nerve impulse at the terminal button, some the vesicles discharge their contents into the narrow cleft that separates the membrane of another cell's dendrite, which is designated to receive the chemical message.
- 95. • Chemical transmitterscarry the signal across synapses • Chemical transmitters are made and stored in the presynaptic terminal • The transmitter diffuses across the synaptic gap and binds to a receptor in the postsynaptic membrane. • Binding of the Transmitter Produces an excitatory postsynaptic potential EPSP or inhibitory postsynaptic potential IPSP
- 96. The Transmitter isBroken down and Recycled • Once the signal has been delivered the transmitter must be removed so that new signals may be received • In some cases the transmitter is broken down by an enzyme in the synapse • In other cases the transmitter is recycled- it is transported back into the presynaptic nerve • In still other cases these 2 methods are combined
- 97. Acetylcholine • Important neurotransmitterin central and peripheral nervous systems. • Acetylcholine is synthesized in the nerve terminal. 1- Acetyl-coenzyme A (AcCoA) is manufacured in mitochondria. 2- Choline is accumulated in the teminals by active uptake from interstitial fluid. 3- AcCoA + choline = acetylcholine.
- 98. Acetylcholine storage • Acetylcholineis stored in vesciles in the verve terminal after its synthesis, each vesicle contains approximatly 104 Ach molecules, which are released as a single packet. Acetylcholine release The arrival of the action potential to the nerve terminal, it leads to increase in the permeability of the terminal to Ca++ influx. • Ca++ recat with synapsin that bind the vesciles, which on its unbinding the vesciles sweeps to attach to the presynaptic membrane. • The vesciles rupture and the acetylcholine released to the synaptic cleft. • Acetylcholine act on its specific receptors on the postsynaptic membrane.
- 99. Acetylcholine release sites 1-Preganglionicnerve fibres of both sympathetic and parasympathetic divisions of the autonomic nervous system. 2-Postganglionic nerves of the parasympathetic division. 3- The sympathetic innervation of sweet glands. 4- Neuromuscular junction. 5- Autonomic ganglion to the adrenal gland.
- 100.
- 101. Acetylcholine inactivation In synapticcleft, Acetylcholinesterase breaks it down into acetate and choline. 50% of choline then re up taken into presynaptic neuron.
- 102. Acetylcholine receptors Acetylcholine effectson the tissue are the result of its action on the receptor present in the membrane of the effector cells. Several types of Ach receptors have been characterized by their sensetivity to agonists (which mimic the action of Ach) or antagonists (which specifically block the action of Ach). • Two types of cholinergic receptors are well known: • Nicotinic receptors which are easily activated by agonist molocule such as nicotine and • Muscarinic receptors: which are sensitive to muscarine.
- 103. Cholinergic receptors Nicotinic receptors (Central) Muscarinicreceptors (peripheral ) Types Two types:- Ganglionic Neruomuscular M1, M2 (cardiac), M3 (glandular&smooth muscle) M4 (brain).M5,M6 and M7. Stimulated by Nicotine in small doses, Ach, metacholine Muscarine, Ach, carbarcholine Blocked by Nicoitin in large doses- decameyhonium d-tubourarine- Atropine scopolamine site Autonomic ganglia M.E.P Adrenal medulla Preganglionic neuron. Parasympathetic (pre-postganglionic) Sympathetic postganglionic nerve endings (sweat glands & skeletal muscle).
- 104. Nicotinic Receptors • Locatedin the ganglia of both the PSNS and SNS • Named “nicotinic” because can be stimulated by the alkaloid nicotine
- 105. Muscarinic Receptors • Locatedpostsynaptically: – Smooth muscle – Cardiac muscle – Glands of parasympathetic fibers – Effector organs of cholinergic sympathetic fibers • Named “muscarinic” because can be stimulated by the alkaloid muscarine
- 106.
- 107. Subdivisions of theAutonomic Nervous System Sympathetic Parasympathetic Primary Neurotransmitter norepinephrine epinephrine (~20%) acetylcholine Receptors & Second Messenger Systems Adrenergic GPCRs α1 – IP3/DAG, ↑[Ca2+ ]i ↑PKC α2 - ↓cAMP/PKA β1 - ↑cAMP/PKA β2 - ↑cAMP/PKA β3 - ↑cAMP/PKA Muscarinic GPCRs M1 – IP3/DAG, ↑[Ca2+ ]i ↑PKC M2 – ↓cAMP/PKA, ↑PI(3)K M3 – ↓cAMP/PKA, IP3/DAG, ↑[Ca2+ ]i ↑PKC M4 – M5 – IP3/DAG, ↑[Ca2+ ]i ↑PKC Adrenal Medulla (epi:norepi::80:20)
- 108. Comparison of sympatheticand Parasympathetic Pathways • Neurotransmitters • Receptors
- 109. Drugs Affecting the AutonomicNervous System Parasympathomimetic drugs: These are drugs which exert an action similar to acetylcholine and there are two types:- - Drugs directly stimulate cholinergic receptors - Drugs inhibit cholinesterase enzyme. Parasympatholytic Drugs: These drugs antagonize the action of acetylcholine.
- 110. Cholinergic Agents • Drugsthat stimulate the parasympathetic nervous system (PSNS). • Drugs that mimic the effects of the PSNS neurotransmitter • Acetylcholine (ACh)
- 111. Parasympathomimetic drugs These aredrugs which exert an action similar to the action of acetylcholine and it is divided into two groups: (A) Drugs that directly stimulate the cholinergic receptors: These include Ach derivatives that not hydrolyzed rapidly by cholinesterase e.g. metacholine, carbachol, poiolocarpine and muscarine. (B) Drugs that inhibit the cholinesterase enzyme: These drugs preserve the action of Ach by preventing the action of cholinesterase enzyme and they are two types:- (1) Drugs which has a reversible effect i.e. their action is temporary e.g. eserine (phyostigmine) and prostigmine (neostigmine). • - Eserine: is a generalized drugs which causes generalized blocking allover the body, thus we use it locally as an eye drops in treatment of glaucoma otherwise it will cause generalized parasympathetic effect. • - Neostigmine:It was used in treatment of myasthenia gravis due to its direct action on the motor end plate. (2) Drugs which have irreversible effect i.e. their action are prolonged e.g. parathion (an insecticide) and D.F.P. (Diisopropyflurophosphate), which is a toxic nerve gas.
- 112. Parasympatholytic Drugs • Thesedrugs which antagonize the action of Ach by one of the following mechanisms:- • Competitive inhibition: These drugs occupy the Ach receptors and present its action. • Persistent depolarization: These drugs cause prolonged depolarization of Ach receptor thus they prevent the excitation of the receptor by the released Ach.
- 113. Parasympatholytic drugs Muscarinic likeaction blockers Ganglion blockers Neuromuscular blocker These drugs block the action of Ach at cholinergic receptors by blocking the action of Ach at muscarinic receptors These drugs block the action of Ach at nicotinic recpotors These drugs block the nicotinic like action of Ach at neuromuscular junction. e.g.- AtropineHomatropine Hyoscine e.g. -Nicotine in large doses. - Arfonad - Hexamethonium e.g. - curare Mechanism of action- competitive inhibition Competitive inhibition. -Persistent depolarization Competitive inhibition. Clinical use: Atropine used for:-- dilation of pupil- relive spasm- prevent bronchial secretion - Ganglion blocker used for blocking conduction in sympathetic ganglion of hypertension. - Curare is used as a muscle relaxant
- 114.
- 115. DHBR NADP+ NADPH from phe, diet,or protein breakdown Tyrosine L-Dopa H2OO2 Tyrosine hydroxylase (rate-determining step) BH2BH4 1 Dopa decarboxylase CO2 Dopamine pyridoxal phosphate 2 Dopamine hydroxylase ascorbate H2O Norepinephrine O2 3 PNMT SAM SAH Epinephrine 4 Biosynthesis of catecholamines. BH2/BH4, dihydro/tetrahydrobiopterin; DHBR, dihydrobiopterin reductase; PNMT, phenylethanolamine N-CH3 transferase; SAH, S- adenosylhomocysteine; SAM, S-adenosylmethionine Parkinson’s disease: local deficiency of dopamine synthesis; L-dopa boosts productionPNMT specific to adrenal medulla SAM from metabolism of Met DPN OHase in neuro- scretory granules
- 116. ........ acetylcholine Adrenal Medulla Chromaffin Cell Neuron Acute regulation Tyrosine L-DopaDPN DPN ↓ NE granule induction Chronic regulation Stress Hypothalamus ACTH Cortisol from adrenal cortex via intra- adrenal portal system Epinephrine PNMT NE neuro- secretory granules E E E NE E Regulation of the release of catecholamines and synthesis of epinephrine in the adrenal medulla chromaffin cell. promotes exocytosis ⊕ ................ E EE ENE E E E NE E Ca2+
- 117. Norepinephrine Epinephrine COMT +MAO Vanillylmandelic acid Degradation of epinephrine, norepinephrine and dopamine via monoamine oxidase (MAO) and catechol O methyl-‑ ‑ transferase (COMT) Neuronal re-uptake and degradation of catecholamines quickly terminates hormonal or neurotransmitter activity. Cocaine binds to dopamine receptor to block re-uptake of dopamine Dopamine continues to stimulate receptors of the postsynaptic nerve. Dopamine Homovanillic acid COMT + MAO
- 118. Table 1. Classificationof Adrenergic Hormone Receptors Receptor Agonists Second Messenger G protein alpha1 (α1 ) E>NE IP3 /Ca2+ ; DAG Gq alpha2 (α2 ) NE>E ↓ cyclic AMP Gi beta1 (β1 ) E=NE ↑ cyclic AMP Gs beta2 (β2 ) E>>NE ↑ cyclic AMP Gs E = epinephrine; NE = norepinephrine Synthetic agonists: isoproterenol binds to beta receptors phenylephrine binds to alpha receptors (nose spray action) Synthetic antagonists: propranolol binds to beta receptors phentolamine binds to alpha receptors
- 119. NH2 HOOC Figure 4. Modelfor the structure of the β2-adrenergic receptor
- 120. Table 2. Metabolicand muscle contraction responses to catecholamine binding to various adrenergic receptors. Responses in italics indicate decreases of the indicated process (i.e., decreased flux through a pathway or muscle relaxation) Process α1 -receptor (IP3 , DAG) α2 - receptor (↓ cAMP) β1 - receptor (↑ cAMP) β2 -receptor (↑ cAMP) Carbohydrat e metabolism ↑ liver glycogenolysis No effect No effect ↑liver/muscle glycogenolysis; ↑ liver gluconeogenesis; ↓ glycogenesis Fat metabolism No effect ↓ lipolysis ↑ lipolysis No effect Hormone secretion No effect ↓ insulin secretion No effect ↑ insulin and glucagon secretion Muscle contraction Smooth muscle - blood vessels, genitourinary tract Smooth muscle - some vascular; GI tract relaxation Myocardial -↑ rate, force Smooth muscle relaxation - bronchi, blood vessels, GI tract, genitourinary tract
- 121. ⊕ β1 or β2 receptor ATPcyclic AMP Gs β γ αs β γ GTP inactive adenylyl cyclase γ β GTP ACTIVE adenylyl cyclase inactive adenylyl cyclase α2 receptor Figure 5. Mechanisms of β1, β2, and α2 agonist effects on adenylyl cyclase activity Gi β γ αi GTP αs GTP αi X
- 122. "FIGHT OR FLIGHT"RESPONSE epinephrine/ norepinephrine major elements in the "fight or flight" response acute, integrated adjustment of many complex processes in organs vital to the response (e.g., brain, muscles, cardiopulmonary system, liver) occurs at the expense of other organs less immediately involved (e.g., skin, GI). epinephrine: rapidly mobilizes fatty acids as the primary fuel for muscle action increases muscle glycogenolysis mobilizes glucose for the brain by ↑ hepatic glycogenolysis/ gluconeogenesis preserves glucose for CNS by ↓ insulin release leading to reduced glucose uptake by muscle/ adipose increases cardiac output norepinephrine elicits responses of the CV system - ↑ blood flow and ↓ insulin secretion.
- 123. OH OP [2] degradation to VMA insulinactivation of protein phosphatase to dephosphorylate enzymes[7] α [5] γ β GTPase αGDP epinephrine phosphorylation of β-receptor by β-ARK decreases activity even with bound hormone OH OH [3] OP OP [4] OPOP binding of β-arrestin further inactivates receptor despite bound hormone AC cAMPATP activated PKA phosphorylates enzymes [6] AMP phosphodiesterase GTP [1] dissociation Figure 6. Mechanisms for terminating the signal generated by epinephrine binding to a β-adrenergic receptor
- 124. Β1 found onheart muscle and in certain cells of the kidney B2 found in certain blood vessels, smooth muscle of airways; found where sympathetic neurons ARE NOT Α1 receptors are found most commonly in sympathetic target tissues A2 receptors are found in the GI tract and pancreas (relaxation)