This document discusses the biosynthesis, storage, release, and effects of catecholamines like adrenaline and noradrenaline in the sympathetic nervous system. It describes the different types of adrenergic receptors (alpha and beta), their molecular effects, locations, and functions. The roles of the receptors in various clinical effects like changes in heart rate, blood pressure, bronchodilation, and metabolism are summarized.

1.  1. Lady Ann L. Francisco
 2. Objectives: Steps of Biosynthesis of Catecholamine Distribution of adrenergic receptors Individual Functions of
Adrenergic receptors All aspects of adrenaline – Dale`s Phenomenon
 3. Neurotransmission in ANS
 4. Noradrenergic transmission Nor-adrenaline is the major neurotransmitter of the Sympathetic system Noradrenergic
neurons are postganglionic sympathetic neurons w ith cell bodies in the sympathetic ganglia They have long axons w hich
end in varicosities w here NA is synthesized and stored
 5. Adrenergic transmission Catecholamines: Natural: Adrenaline, Noradrenaline, Dopamine Synthetic: Isoprenaline,
Dobutamine Non-Catecholamines: Ephedrine, Amphetamines, Phenylepherine, Methoxamine, Mephentermine Also
called sympathomimetic amines as most of them contain an intact or partially substituted amino (NH2) group
 6. • Catecholamines: Compounds containing a catechol nucleus (Benzene ring w ith 2 adjacent OH groups) and an amine
containing side chain • Non-catecholamines lack hydroxyl (OH) group
 7. Biosynthesis of Catecholamines Phenylalanine PH Rate limiting Enzyme 5-HT, alpha Methyldopa Alpha-methyl-p-
tyrosine
 8. Storage of Noradrenaline
 9. Release of NA – Feedback Control
 10. Regulators of NA release
 11. Uptake of Catecholamines
 12. Reuptake Sympathetic nerves take up amines and release them as neurotransmitters Uptake I is a high efficiency
system more specific for NA Located in neuronal membrane Inhibited by Cocaine, TCAD, Amphetamines Uptake 2 is less
specific for NA Located in smooth muscle/ cardiac muscle Inhibited by steroids/ phenoxybenzamine No Physiological or
Pharmacological importance
 13. Metabolism of CAs Mono Amine Oxidase (MAO) Intracellular bound to mitochondrial membrane Present in NA
terminals and liver/ intestine MAO inhibitors are used as antidepressants Catechol-o-methyl-transferase (COMT)
Neuronal and non-neuronal tissue Acts on catecholamines and byproducts VMA levels are diagnostic for tumours
 14. Metabolism of CAs (Homovanillic acid) (Vanillylmandelic acid)
 15. Adrenergic neurotransmission
 16. Adrenergic Receptors Adrenergic receptors (or adrenoceptors) are a class of G-protein coupled receptors that are the
target of catecholamines Adrenergic receptors specifically bind their endogenous ligands – catecholamines (adrenaline
and noradrenline) Increase or decrease of 2nd messengers cAMP or IP3/DAG Many cells possess these receptors, and
the binding of an agonist w ill generally cause the cell to respond in a flight- fight manner. For instance, the heart w ill start
beating quicker and the pupils w ill dilate
 17. How Many of them ???? Alpha (α) Beta (β) Adenoreceptors α 1 β3β 2β1α 2 α 2B α 2Cα 2A α 1A α 1B α 1D
 18. Differences - Adrenergic Receptors (α and β) ! Alpha (α) and Beta (β) Agonist affinity of alpha (α): adrenaline >
noradrenaline > isoprenaline Antagonist: Phenoxybenzamine IP3/DAG, cAMP and K+ channel opening Agonist affinity of
beta (β): isoprenaline > adrenaline > noradrenaline Propranolol cAMP and Ca+ channel opening
 19. Potency of catecholamines on Adrenergic Receptors Adr NA Iso Iso Adr NA Log Concentration Aortic strip contraction
Bronchial relaxation α β
 20. Molecular Effector Differences - α Vs β α Receptors: ○ IP3/DAG ○ cAMP ○ K+ channel opening β Receptors: ○ cAMP
○ Ca+ channel opening
 21. Recall: Adenylyl cyclase: cAMP pathw ay PKA Phospholamban Increased Interaction w ith Ca++ Faster relaxation
Troponin Cardiac contractility Other Functional proteins PKA alters the functions of many Enzymes, ion channels,
transporters and structural proteins. Faster sequestration of Ca++ in SR

2.  22. PKc Also Recall: Phospholipase C: IP3-DAG pathw ay
 23. Differences betw een β1, β2 and β3 Beta-1 Beta-2 Beta-3 Location Heart and JG cells Bronchi, uterus, Blood vessels,
liver, urinary tract, eye Adipose tissue Agonist Dobutamine Salbutamol - Antagonist Metoprolol, Atenolol Alpha-methyl
propranolol - Action on NA Moderate Weak Strong
 24. Clinical Effects of β-receptor stimulation β1: Adrenaline, NA and Isoprenaline: Tachycardia Increased myocardial
contractility Increased Lipolysis Increased Renin Release β2: Adrenaline and Isoprenaline (not NA) Bronchi – Relaxation
SM of Arterioles (skeletal Muscle) – Dilatation Uterus – Relaxation Skeletal Muscle – Tremor Hypokalaemia Hepatic
Glycogenolysis and hyperlactiacidemia β3: Increased Plasma free fatty acid – increased O2 consumption - increased heat
production
 25. Differences betw een α1 and α2 Alpha-1 Alpha-2 Location Post junctional – blood vessels of skin and mucous
membrane, Pilomotor muscle & sw eat gland, radial muscles of Iris Prejunctional Function Stimulatory – GU,
Vasoconstriction, gland secretion, Gut relaxation, Glycogenolysis Inhibition of transmitter release, vasoconstriction,
decreased central symp. Outflow , platelet aggregation Agonist Phenylephrine, Methoxamine Clonidine Antagonist
Prazosin Yohimbine
 26. α1 adrenoceptors Clinical effects Eye -- Mydriasis Arterioles – Constriction (rise in BP) Uterus -- Contraction Skin --
Sw eat Platelet - Aggregation Male ejaculation Hyperkalaemia Bladder Contraction α2 adrenoceptors on nerve endings
mediate negative feedback w hich inhibits noradrenaline release
 27. Molecular Basis of Adrenergic Receptors Also glycogenolysis in liver Inhibition of Insulin release and Platelet
aggregation Gluconeogen esis
 28. Dopamine receptors D1-receptors are post synaptic receptors located in blood vessels and CNS D2-receptors are
presynaptic present in CNS, ganglia, renal cortex
 29. Summary of agents modifying adrenergic transmission Step Actions Drug Synthesis of NA Inhibition α - methyl-p-
tyrosine Axonal uptake Block Cocaine, guanethidine, ephedrine Vesicular uptake Block Reserpine Vesicular NA
Displacement Guanethidine Membrane NA pool Exchange diffusion Tyramine, Ephedrine Metabolism MAO-A inhibition
MAO-B inhibition COMT inhibition Moclobemide Selegiline Tolcapone Receptors α 1 α 2 β1 + β2 β1 Prazosin Yohimbine
Propranolol Metoprolol
 30. Adrenaline as prototype Potent stimulant of alpha and beta receptors Complex actions on targets: Heart, Blood
vessel, Blood pressure(dale’s phenomenon)
 31. Dale`s Vasomotor Reversal Phenomenon
 32. CNS Skeletal Muscle  Uterus  Bladder  GIT  Respiratory Actions of Adrenaline
 33. Metabolic effects Increases concentration of glucose and lactic acid Calorigenesis (β-2 and β-3) Inhibits insulin
secretion (α-2) Decreases uptake of glucose by peripheral tissue Simulates glycogenolysis - Beta effect Increases free
fatty acid concentration in blood Hypokalaemia – initial hyperkalaemia
 34. ADME All Catecholamines are ineffective orally Absorbed slow ly from subcutaneous tissue Faster from IM site
Inhalation is locally effective Not usually given IV Rapidly inactivated in Liver by MAO and COMT
 35. ADRs Restlessness, Throbbing headache, Tremor, Palpitations Cerebral hemorrhage, cardiac arrhythmias
Contraindicated in hypertensives, hyperthyroid and angina poctoris Halothane and beta-blockers – not indicated