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PRESENTATION ON
NEUROTRANSMISSION AND
NON ADRENERGIC NON
CHOLINERGIC
NEUROTRANSMISSION
1
Department of Pharmacology
BVVS COP BGK
❖Neurotransmission:- It is the process that mediates
the functional interaction between two neurons and other
cell types skeletal muscle and smooth muscle.
❖The transmission of nerve impulses between neurons or a
between a neuron and a muscle fiber or other structures.
❖Process in which signaling molecules called
neurotransmitters are released by axon terminal of neuron
and bind with the dendrites of another neuron.
❖Neurons are pretty long and measure above 1m in length.
❖Neurotransmission occurs in specialized region called
Synapse. It is a structure that permits a neuron to pass an
electrical or chemical signal to another neuron or to target
cell.
2
Department of Pharmacology
BVVS COP BGK
AXONAL TERMINAL
3
Department of Pharmacology
BVVS COP BGK
➢The electrical signal can not jump over the gap. At the
synaptic cleft the electrical signal translate into chemical
message by neurotransmitters.
❖Neurotransmitters:- It is chemicals enables
neurotransmission.
➢Glutamate & Aspartate are major neurotransmitter in
CNS.
➢Gamma Amino Butyric Acid [GABA] in brain.
➢Serotonin, Acetylcholine, Dopamine are the other
neurotransmitters.
➢The chemical swims (Diffuse) across synaptic cleft until
it reaches other neuron.
➢The other neuron then translate chemical signal back to
the electrical one and some chemical message is then
degraded.
4
Department of Pharmacology
BVVS COP BGK
5
Department of Pharmacology
BVVS COP BGK
6
Department of Pharmacology
BVVS COP BGK
❖Steps involved in Neurotransmission:-
1)Synthesis of the neurotransmitter. This can take place in the cell
body, in the axon or in the axon terminal.
2)Storage of the neurotransmitter in storage granules or vesicles in
the axon terminal.
3)Calcium enters the axon terminal during an action potential
causing release of neurotransmitter into synaptic cleft.
4)After its release the transmitter binds and activates a receptor in the
postsynaptic membrane.
5)Deactivation of neurotransmitter. The neurotransmitter is either
destroyed enzymatically or taken up back into the terminal from
which it came, where it can be reused or degraded and removed. 7
Department of Pharmacology
BVVS COP BGK
8
Department of Pharmacology
BVVS COP BGK
Step 1 : Neurotransmitter Synthesis
❖The neurotransmitters are large peptides or smaller
amines.
❖The large peptides synthesized in the cell body of
neuron and translated to synaptic terminal through
axon.
❖The smaller amines/amino acid can generally
synthesized at presynaptic terminal itself.
9
Department of Pharmacology
BVVS COP BGK
Step 2 & 3 : Neurotransmitter packaging & release
❖ Once the neurotransmitter synthesized they need to put
in small groups ready to launch across the synaptic cleft
means neurotransmitter need to be packaged into
vesicles. The neurotransmitters released into synaptic
cleft when they receive an order from Ca2+
ions to do so.
❖ When a electrical signal reached the presynaptic
terminal it opens some channel in membrane (these are
called volted gated Ca2+
channels)
❖ Once channels are open calcium ion from surrounding
rush into the presynaptic terminal.
10
Department of Pharmacology
BVVS COP BGK
Step 4 : Neurotransmitter binding
❖ The neurotransmitter can swim ‘diffuse’ through the
synaptic cleft reach the post synaptic neuron.
❖ The membrane of post synaptic neuron continue few
channels (receptors) that control how a neurotransmitter
can be translated into an electrical signal.
11
Department of Pharmacology
BVVS COP BGK
Step 5 : Stopping the chemical signal
❖ When neurotransmitter signal translated into electrical
signal. The post synaptic receptors needed to be cleared
very quickly so they can receive new signals.
❖ Some neurotransmitters will be degraded and some will
transported back to the presynaptic terminal and
sometimes they are absorbed by postsynaptic terminal.
12
Department of Pharmacology
BVVS COP BGK
❖Co Transmission :
✓ Co transmission is transmission through a single synapse
by means of more than one transmitter.
Ex:- To elicit vasoconstriction post ganglionic
sympathetic neurons release their classical transmitter
nor-adrenaline as well as ATP.
13
Department of Pharmacology
BVVS COP BGK
✓ Many peripheral and central neuron have been shown to
release more than one active substance when stimulated.
✓ In ANS beside Primary transmitter Ach and NA neurones
have been found to be elaborate purines [ATP, Adenosine],
Peptides, Nitric oxide, Prostaglandins as a co-transmitters.
✓ In most autonomic cholinergic neurons VIP [Vasoactive
Intestinal Peptide] associate with Ach. While ATP is
associated with both Ach and NA. The co-transmitter is
stored in the same neuron but in distinct synaptic vesicles or
locations.
✓ ATP, Adenosine, VIP, Substance P, Somatostatin, NO, PG,
these are released with combination with major
neurotransmitter like NA & Ach.
➢ NA + ATP in Vas difference and blood vessels
➢ NA + NPY in blood vessels
➢ VIP + Ach in salivary gland
14
Department of Pharmacology
BVVS COP BGK
✓ Noradrenergic, Non-cholinergic [NANC] transmission
has been demonstrated in urinary tract, salivary glands
and in some blood vessels. By co-transmission many
anomalous findings have been revealed.
✓ATP is stored with NA in same vesicles on being
released by nerve impulse it may.
✓ Serve to regulate the presynaptic release of primary
transmitter or postsynaptic sensitivity to it.
✓Co-transmitter may influence on the synaptic structures.
15
Department of Pharmacology
BVVS COP BGK
NON ADRENERGIC
NON CHOLINERGIC
NEUROTRANSMISSION
Department of Pharmacology BVVS COP BGK
NEUROTRANSMISSION
Non-adrenergic non-cholinergic neurotransmission
➢A non-adrenergic non cholinergic transmitter [NANC] is a
neurotransmitter of the nervous system (ANS), that is neither
acetylcholine, or nor-epinephrine.
➢ They secret neither Ach or NE. They can also secret transmitter
such as VIP (Vasoactive intestinal peptide), substance P, NO (Nitric
Oxide), ATP along with Ach & NE.
➢ Non adrenergic non cholinergic transmission describes a part of
the autonomic nervous system which does not use acetylcholine or
nor-adrenaline as transmitters.
➢ NANC transmitter, which are released together with acetylcholine
or nor adrenaline.
17
Department of Pharmacology BVVS COP BGK
a. Class amino acid and amino acid derivatives:-
ex: Glutamate, Aspartate, Glycine, Histamine, GABA
b. Class Purines-
ex: Adenosine, ATP
c. Class Gas-
ex: Nitric oxide
❖In most autonomic cholinergic neurons, VIP (Vasoactive
Intestinal Peptide) associate with Ach. While ATP is
associated with both Ach and NE.
18
Department of Pharmacology BVVS COP BGK
19
Department of Pharmacology BVVS COP BGK
➢ Glutamate:-
➢ It is non essential amino acid.
➢ Excitatory neurotransmitter, stored in neuronal cell
membrane.
➢Glutamate is produced in the human body and plays an
important role in metabolism.
➢Almost two kilograms (about four pounds) of naturally
occurring glutamate are found in muscles, Brain, Kidneys,
liver, and in other organs and tissues.
➢Glutamate comes into the CNS mainly by glial cells and
Kreb’s cycle.
20
Department of Pharmacology BVVS COP BGK
➢ Synthesis:-
➢Glutamate comes into the CNS mainly by glial cells and Kreb’s
cycle.
➢In the neuron the glutamine is converted into glutamate with the
help of glutaminase enzyme.
➢Glutamate is stored in the synaptic vesicles.
➢From synaptic vesicles glutamate release by the process of
exocytosis.
21
Department of Pharmacology BVVS COP BGK
SYNTHESIS, RELEASE, REUPTAKE OF GLUTAMATE
22
Department of Pharmacology BVVS COP BGK
23
Department of Pharmacology BVVS COP BGK
Receptors of Glutamate
24
Department of Pharmacology BVVS COP BGK
A. Ionotropic Receptor:-
➢All the ionotropic receptors are composed of 4 subunits.
➢Ligand gated non selective cation channels.
➢Allows flow of K+, Na+ and sometimes Ca+ in response
to glutamate binding.
a.AMPA Receptors (α-amino-3-hydroxyl-5-methyl-4-
isoxazolepropinoic acid):-
➢AMPA receptors are present on all neurons.
➢GluR1- GluR4 subunits.
➢The majority of AMPA receptors contain the GluA2
subunit and are permeable to Na+ and K+ but not to Ca+.
25
Department of Pharmacology BVVS COP BGK
b. Kainate Receptors:-
➢Kainate receptors are expressed at high levels in the
hippocampus, cerebellum and spinal cord.
➢They are formed from a number of subunit combination
GluK1-GluK5.
➢Kainate receptors are permeable to Na+ and K+ and some
subunit combinations also for Ca+.
26
Department of Pharmacology BVVS COP BGK
c. NMDA receptors (N-methyl-D-aspartate):
➢NMDA receptors are present on all neurons in the CNS.
➢All NMDA receptors require the presence of the subunit
GluN1.
➢The channel also contains two NR2 subunits:- GluN2A-
GluN2D.
➢All NMDA receptors are highly permeable to Ca2+, as
well as Na+ and K+.
➢AMPA and kainate receptors activation results in channel
opening at resting membrane potential, whereas NMDA
receptor activation does not.
➢This is due to the voltage dependent block of the NMDA
pore by extracellular Mg2+.
27
Department of Pharmacology BVVS COP BGK
B. Metabotropic glutamate receptors:
➢Group 1 Receptors are typically located post synaptically.
➢They cause excitation by activating a non-selective cation
channel.
➢Group 2 and Group 3 receptors are typically located on
presynaptic nerve terminals.
➢Activation of these receptors causes the inhibition of
transmitter release.
28
Department of Pharmacology BVVS COP BGK
29
Department of Pharmacology BVVS COP BGK
✓ Disorders:
1. Bipolar depression
2. Huntington’s disease
3. Alzheimer’s disease
4. Neurodegenerative Disorders
5. ALS ( Amyotrophic Lateral Sclerosis)
6. Stroke and trauma
7. Epilepsy
30
Department of Pharmacology BVVS COP BGK
✓ Uses:
➢Glutamate plays an imp role in,
➢Memory, Learning
31
Department of Pharmacology BVVS COP BGK
THANK U
32
Department of Pharmacology BVVS COP BGK

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Presentation on neurotransmission and noradrealine norcholinergic (nanc) converted

  • 1. PRESENTATION ON NEUROTRANSMISSION AND NON ADRENERGIC NON CHOLINERGIC NEUROTRANSMISSION 1 Department of Pharmacology BVVS COP BGK
  • 2. ❖Neurotransmission:- It is the process that mediates the functional interaction between two neurons and other cell types skeletal muscle and smooth muscle. ❖The transmission of nerve impulses between neurons or a between a neuron and a muscle fiber or other structures. ❖Process in which signaling molecules called neurotransmitters are released by axon terminal of neuron and bind with the dendrites of another neuron. ❖Neurons are pretty long and measure above 1m in length. ❖Neurotransmission occurs in specialized region called Synapse. It is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to target cell. 2 Department of Pharmacology BVVS COP BGK
  • 3. AXONAL TERMINAL 3 Department of Pharmacology BVVS COP BGK
  • 4. ➢The electrical signal can not jump over the gap. At the synaptic cleft the electrical signal translate into chemical message by neurotransmitters. ❖Neurotransmitters:- It is chemicals enables neurotransmission. ➢Glutamate & Aspartate are major neurotransmitter in CNS. ➢Gamma Amino Butyric Acid [GABA] in brain. ➢Serotonin, Acetylcholine, Dopamine are the other neurotransmitters. ➢The chemical swims (Diffuse) across synaptic cleft until it reaches other neuron. ➢The other neuron then translate chemical signal back to the electrical one and some chemical message is then degraded. 4 Department of Pharmacology BVVS COP BGK
  • 7. ❖Steps involved in Neurotransmission:- 1)Synthesis of the neurotransmitter. This can take place in the cell body, in the axon or in the axon terminal. 2)Storage of the neurotransmitter in storage granules or vesicles in the axon terminal. 3)Calcium enters the axon terminal during an action potential causing release of neurotransmitter into synaptic cleft. 4)After its release the transmitter binds and activates a receptor in the postsynaptic membrane. 5)Deactivation of neurotransmitter. The neurotransmitter is either destroyed enzymatically or taken up back into the terminal from which it came, where it can be reused or degraded and removed. 7 Department of Pharmacology BVVS COP BGK
  • 9. Step 1 : Neurotransmitter Synthesis ❖The neurotransmitters are large peptides or smaller amines. ❖The large peptides synthesized in the cell body of neuron and translated to synaptic terminal through axon. ❖The smaller amines/amino acid can generally synthesized at presynaptic terminal itself. 9 Department of Pharmacology BVVS COP BGK
  • 10. Step 2 & 3 : Neurotransmitter packaging & release ❖ Once the neurotransmitter synthesized they need to put in small groups ready to launch across the synaptic cleft means neurotransmitter need to be packaged into vesicles. The neurotransmitters released into synaptic cleft when they receive an order from Ca2+ ions to do so. ❖ When a electrical signal reached the presynaptic terminal it opens some channel in membrane (these are called volted gated Ca2+ channels) ❖ Once channels are open calcium ion from surrounding rush into the presynaptic terminal. 10 Department of Pharmacology BVVS COP BGK
  • 11. Step 4 : Neurotransmitter binding ❖ The neurotransmitter can swim ‘diffuse’ through the synaptic cleft reach the post synaptic neuron. ❖ The membrane of post synaptic neuron continue few channels (receptors) that control how a neurotransmitter can be translated into an electrical signal. 11 Department of Pharmacology BVVS COP BGK
  • 12. Step 5 : Stopping the chemical signal ❖ When neurotransmitter signal translated into electrical signal. The post synaptic receptors needed to be cleared very quickly so they can receive new signals. ❖ Some neurotransmitters will be degraded and some will transported back to the presynaptic terminal and sometimes they are absorbed by postsynaptic terminal. 12 Department of Pharmacology BVVS COP BGK
  • 13. ❖Co Transmission : ✓ Co transmission is transmission through a single synapse by means of more than one transmitter. Ex:- To elicit vasoconstriction post ganglionic sympathetic neurons release their classical transmitter nor-adrenaline as well as ATP. 13 Department of Pharmacology BVVS COP BGK
  • 14. ✓ Many peripheral and central neuron have been shown to release more than one active substance when stimulated. ✓ In ANS beside Primary transmitter Ach and NA neurones have been found to be elaborate purines [ATP, Adenosine], Peptides, Nitric oxide, Prostaglandins as a co-transmitters. ✓ In most autonomic cholinergic neurons VIP [Vasoactive Intestinal Peptide] associate with Ach. While ATP is associated with both Ach and NA. The co-transmitter is stored in the same neuron but in distinct synaptic vesicles or locations. ✓ ATP, Adenosine, VIP, Substance P, Somatostatin, NO, PG, these are released with combination with major neurotransmitter like NA & Ach. ➢ NA + ATP in Vas difference and blood vessels ➢ NA + NPY in blood vessels ➢ VIP + Ach in salivary gland 14 Department of Pharmacology BVVS COP BGK
  • 15. ✓ Noradrenergic, Non-cholinergic [NANC] transmission has been demonstrated in urinary tract, salivary glands and in some blood vessels. By co-transmission many anomalous findings have been revealed. ✓ATP is stored with NA in same vesicles on being released by nerve impulse it may. ✓ Serve to regulate the presynaptic release of primary transmitter or postsynaptic sensitivity to it. ✓Co-transmitter may influence on the synaptic structures. 15 Department of Pharmacology BVVS COP BGK
  • 17. NEUROTRANSMISSION Non-adrenergic non-cholinergic neurotransmission ➢A non-adrenergic non cholinergic transmitter [NANC] is a neurotransmitter of the nervous system (ANS), that is neither acetylcholine, or nor-epinephrine. ➢ They secret neither Ach or NE. They can also secret transmitter such as VIP (Vasoactive intestinal peptide), substance P, NO (Nitric Oxide), ATP along with Ach & NE. ➢ Non adrenergic non cholinergic transmission describes a part of the autonomic nervous system which does not use acetylcholine or nor-adrenaline as transmitters. ➢ NANC transmitter, which are released together with acetylcholine or nor adrenaline. 17 Department of Pharmacology BVVS COP BGK
  • 18. a. Class amino acid and amino acid derivatives:- ex: Glutamate, Aspartate, Glycine, Histamine, GABA b. Class Purines- ex: Adenosine, ATP c. Class Gas- ex: Nitric oxide ❖In most autonomic cholinergic neurons, VIP (Vasoactive Intestinal Peptide) associate with Ach. While ATP is associated with both Ach and NE. 18 Department of Pharmacology BVVS COP BGK
  • 20. ➢ Glutamate:- ➢ It is non essential amino acid. ➢ Excitatory neurotransmitter, stored in neuronal cell membrane. ➢Glutamate is produced in the human body and plays an important role in metabolism. ➢Almost two kilograms (about four pounds) of naturally occurring glutamate are found in muscles, Brain, Kidneys, liver, and in other organs and tissues. ➢Glutamate comes into the CNS mainly by glial cells and Kreb’s cycle. 20 Department of Pharmacology BVVS COP BGK
  • 21. ➢ Synthesis:- ➢Glutamate comes into the CNS mainly by glial cells and Kreb’s cycle. ➢In the neuron the glutamine is converted into glutamate with the help of glutaminase enzyme. ➢Glutamate is stored in the synaptic vesicles. ➢From synaptic vesicles glutamate release by the process of exocytosis. 21 Department of Pharmacology BVVS COP BGK
  • 22. SYNTHESIS, RELEASE, REUPTAKE OF GLUTAMATE 22 Department of Pharmacology BVVS COP BGK
  • 24. Receptors of Glutamate 24 Department of Pharmacology BVVS COP BGK
  • 25. A. Ionotropic Receptor:- ➢All the ionotropic receptors are composed of 4 subunits. ➢Ligand gated non selective cation channels. ➢Allows flow of K+, Na+ and sometimes Ca+ in response to glutamate binding. a.AMPA Receptors (α-amino-3-hydroxyl-5-methyl-4- isoxazolepropinoic acid):- ➢AMPA receptors are present on all neurons. ➢GluR1- GluR4 subunits. ➢The majority of AMPA receptors contain the GluA2 subunit and are permeable to Na+ and K+ but not to Ca+. 25 Department of Pharmacology BVVS COP BGK
  • 26. b. Kainate Receptors:- ➢Kainate receptors are expressed at high levels in the hippocampus, cerebellum and spinal cord. ➢They are formed from a number of subunit combination GluK1-GluK5. ➢Kainate receptors are permeable to Na+ and K+ and some subunit combinations also for Ca+. 26 Department of Pharmacology BVVS COP BGK
  • 27. c. NMDA receptors (N-methyl-D-aspartate): ➢NMDA receptors are present on all neurons in the CNS. ➢All NMDA receptors require the presence of the subunit GluN1. ➢The channel also contains two NR2 subunits:- GluN2A- GluN2D. ➢All NMDA receptors are highly permeable to Ca2+, as well as Na+ and K+. ➢AMPA and kainate receptors activation results in channel opening at resting membrane potential, whereas NMDA receptor activation does not. ➢This is due to the voltage dependent block of the NMDA pore by extracellular Mg2+. 27 Department of Pharmacology BVVS COP BGK
  • 28. B. Metabotropic glutamate receptors: ➢Group 1 Receptors are typically located post synaptically. ➢They cause excitation by activating a non-selective cation channel. ➢Group 2 and Group 3 receptors are typically located on presynaptic nerve terminals. ➢Activation of these receptors causes the inhibition of transmitter release. 28 Department of Pharmacology BVVS COP BGK
  • 30. ✓ Disorders: 1. Bipolar depression 2. Huntington’s disease 3. Alzheimer’s disease 4. Neurodegenerative Disorders 5. ALS ( Amyotrophic Lateral Sclerosis) 6. Stroke and trauma 7. Epilepsy 30 Department of Pharmacology BVVS COP BGK
  • 31. ✓ Uses: ➢Glutamate plays an imp role in, ➢Memory, Learning 31 Department of Pharmacology BVVS COP BGK
  • 32. THANK U 32 Department of Pharmacology BVVS COP BGK