Non-adrenergic, non-cholinergic (NANC) neurotransmitters play important roles in synaptic transmission beyond acetylcholine and noradrenaline. NANC neurotransmitters include purines like ATP and adenosine, peptides, nitric oxide, and prostaglandins. These neurotransmitters are released from neurons and can regulate the release and effects of the primary neurotransmitters as well as have direct effects on their own. Common NANC transmitters in the autonomic nervous system include VIP, NPY, endothelins, CGRP, and ATP which have various effects on smooth muscle, blood vessels, and other tissues.

1. NON-ADRENERGIC, NON-
CHOLINERGIC (NANC)
TRANSMITTERS
PRESENTER- DR. RAHUL VAISH
GUIDE- DR. REKHA
1

2. The neurotransmitters other than acetylcholine and
noradrenaline of sympathetic and parasympathetic nervous
systems play important roles in synaptic junction
transmission, and these neurotransmitters are generally
called Non-Adrenergic, Non-Cholinergic (NANC)
neurotransmitters.
INTRODUCTION
2

3. INTRODUCTION
 Smooth muscle of many tissues that are innervated by the
autonomic nervous system shows inhibitory junction potentials.
Such responses frequently are undiminished in the presence of
adrenergic and muscarinic cholinergic antagonists, these
observations have been taken as evidence for the existence of
NANC transmission in the autonomic nervous system.
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4.  Currò D et al stated that at around 1960s Burnstock and his
team were the first set of neurophysiologists that discovered
NANC neurotransmission and inhibitory junction potentials
(IJP).
 Effect of NANC motor functions demonstrated in autonomic
innervation of cardiovascular, genitourinary, respiratory and
most especially gastrointestinal system.
 Joos GF stated that most bronchodilation of the airway are as
a result of inhibitory NANC transmitters, predominantly VIP
and NO.
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5. It has now become apparent that the classical ‘one neuron—one
transmitter’ model is an over simplification.
Most peripheral and central neurons on stimulation have been
shown to release more than one active substance.
In the ANS, besides the primary transmitters ACh and NA,
neurones have been found to elaborate purines (ATP,
adenosine), peptides (vasoactive intestinal peptide or VIP,
neuropeptide-Y or NPY, substance P, enkephalins, somatostatin,
etc.), nitric oxide (NO) and prostaglandins as co-transmitters.
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6. In most autonomic cholinergic neurons VIP is associated with Ach ,
while ATP is associated with both ACh and NA.
Vascular adrenergic nerves contain NPY which causes long lasting
vasoconstriction.
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7. 7
On being release NANC transmitters serve
to regulate
 Prejunctional/presynaptic release of
primary NT`s
 Postsynaptic sensitivity– neuro
modulatory role
Serves as an alternative transmitter &
exerts a tropic influence on the synaptic
structure.
Eg: dopamine, enkephalins,
somatostatin, VIP, NYP, ATP,PG`s,
NO, GABA & substance P

8. Time-course of action of the primary transmitter and the co-
transmitter is usually different.
 Co-transmitter VIP of parasympathetic neurons produces a slow
and long-lasting response, while another one (NO) has an
intermediate time-course of action between VIP and ACh (fast
acting).
 In sympathetic neurons, the co-transmitter NPY is slower acting
and ATP faster acting than NA.
 Co-transmitters like NO, VIP, NPY diffuse to a wider area, and can
affect receptors at some distance from the site of release.
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10. 10

11. Vasoactive peptides are autacoids with significant actions on vascular smooth muscle as
well as other tissues.
They include vasoconstrictors, vasodilators, and peptides with mixed effects.
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12. ENDOTHELINS
oEndothelin's are peptide vasoconstrictors formed in and released by
endothelial cells in blood vessels.
oFunction as autocrine and paracrine hormones in the vasculature
oThree endothelin peptides (ET-1, ET-2, and ET-3)
oTwo receptors, ETA and ETB
oETA receptor appears to be responsible for the vasoconstriction produced
by endothelin’s.
oEndothelin's are much more potent than norepinephrine as vasoconstrictors
and have a relatively long-lasting effect.
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13. It stimulate the heart, increase natriuretic peptide release, and
activate smooth muscle proliferation.
ETA antagonists available for the treatment of pulmonary
hypertension include bosentan and ambrisentan.
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14. NPY (neuropeptide Y)
•NPY (neuropeptide Y) is a potent vasoconstrictor peptide that also
stimulates the heart.
•NPY is found in the CNS and peripheral nerves.
•It is commonly localized as a co-transmitter in adrenergic nerve endings.
•In experimental animals, NPY administered in the CNS stimulates feeding
and causes hypotension and hypothermia.
•Peripheral administration causes positive chronotropic and inotropic effects
in the heart and hypertension.
•Several receptor subtypes have been identified, but neither agonists nor
antagonists of this peptide have found clinical application.
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15. VIP (vasoactive intestinal peptide
It is an extremely potent vasodilator but is probably more
important as a neurotransmitter.
It is found in the central and peripheral nervous systems and
in the gastrointestinal tract.
No clinical application has been found for this peptide.
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16. Neurokinins (substance P,
neurokinin A, and neurokinin B)
They act at NK1 and NK2 receptors in the central nervous system (CNS) and the
periphery.
Substance P has mixed vascular effects.
It is a potent arteriolar vasodilator and a potent stimulant of veins and intestinal
and airway smooth muscle.
Function as a local hormone in the gastrointestinal tract.
Highest concentrations of substance P are found in the parts of the nervous
system that contain neurons sub serving pain.
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17.  Capsaicin, the “hot” component of chili peppers, releases
substance P from its stores in nerve endings and depletes the
peptide.
Capsaicin has been approved for topical use on arthritic joints
and for post-herpetic neuralgia.
Neurokinins appear to be involved in certain CNS conditions,
including depression and nausea and vomiting.
Aprepitant is an oral antagonist at NK1 receptors and is
approved for use in chemotherapy-induced nausea and vomiting.
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18. CGRP (calcitonin gene-related peptide)
It is found (along with calcitonin) in high concentrations in the thyroid but
it also present in most smooth muscle tissues.
The presence of CGRP in smooth muscle suggests a function as a co-
transmitter in autonomic nerve endings.
CGRP is the most potent hypotensive agent discovered to date and causes
reflex tachycardia.
 Some evidence suggests that CGRP is involved in migraine headache.
Currently, there is no clinical application for this peptide.
However, an oral CGRP antagonist, if available, would be of great interest
for the treatment of migraine.
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20. PURINERGIC RECEPTORS
Three main types of purine receptor are:
1. Adenosine receptors (A1, A2A, A2B and A3), formerly known as
P1 receptors, which are Gpcr that regulate cAMP.
2. P2Y metabotropic receptors (P2Y1–14), which are Gpcr that utilize
either cAMP or phospholipase C activation as their signaling system
they respond to various adenine nucleotides, generally preferring
ATP over ADP or AMP.
3. P2X ionotropic receptors (P2X1–7) which are multimeric ATP-
gated cation channels.
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21. PURINERGIC RECEPTORS
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22. 22

23. ADENOSINE AS A MEDIATOR
Simplest form the purines, adenosine is found in biological
fluids throughout the body.
 It exists free in the cytosol of all cells and is transported in and
out mainly by a membrane transporter.
Adenosine in tissues comes partly from this intracellular
source and partly from extracellular hydrolysis of released
ATP or ADP
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24. ADENOSINE AND THE CARDIOVASULAR SYSTEM
Adenosine inhibits cardiac conduction and it is likely that all four of the
adenosine receptors are involved in this effect.
Due to this, adenosine itself used as a drug, being given as an intravenous
bolus injection to terminate supraventricular tachycardia.
Adenosine uptake is blocked (and thus its action prolonged) by
dipyridamole, a vasodilator and antiplatelet drug.
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25. ADENOSINE AND ASTHMA
Adenosine by acting through its A1 receptor, it promotes mediator
release from mast cells, and causes enhanced mucus secretion,
bronchoconstriction and leukocyte activation.
 Methylxanthines, especially analogues of theophylline are adenosine
receptor antagonists.
Theophylline has been used for the treatment of asthma and part of its
beneficial activity may be ascribed to its antagonism of the A1 receptor.
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26. However, methylxanthines also increase cAMP by inhibiting
phosphodiesterase, which contributes to their pharmacological
actions independently of adenosine receptor antagonism.
Certain derivatives of theophylline are claimed to show
greater selectivity for adenosine receptors over
phosphodiesterase.
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27. ADENOSINE IN THE CNS
It Act through A1 and A2A receptors.
Adenosine has an inhibitory effect on many CNS neurons.
Stimulation experienced after consumption of
methylxanthines such as caffeine occurs partly as a result of
block of these receptors.
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28. ADP AND PLATELETS
Secretory vesicles of blood platelets store both ATP and ADP in
high concentrations, and release them when the platelets are
activated.
One of the many effects of ADP is to promote platelet aggregation.
Receptor involved is P2Y12.
Clopidogrel, prasugrel and ticlopidine, are P2Y12 antagonists and
exert their antiaggregating effects through this mechanism.
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29. Adenosine triphosphate (ATP)
ATP exerts its action primarily through the P2X receptors.
ATP is present in all cells in millimolar concentrations and is
released, independently of exocytosis, if the cells are damaged.
The role of intracellular ATP in controlling membrane
potassium channels, which is important in the control of vascular
smooth muscle and of insulin secretion.
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30. It effects include the relaxation of intestinal smooth muscle evoked by
sympathetic stimulation, and contraction of the bladder produced by
parasympathetic nerve.
Burnstock and his colleagues have shown that ATP is released on nerve
stimulation in a Ca2+ -dependent fashion, and that exogenous ATP, in
general, mimics the effects of nerve stimulation in various preparations.
 ATP functions as a conventional ‘fast’ transmitter in the CNS and in
autonomic ganglia.
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31. ATP IN NOCICEPTION
ATP causes pain when injected, as a result of activation of
P2X2 and/or P2X3 receptors in afferent neurons involved in the
transduction of nociception.
 Same receptors seem to be involved in taste perception on the
tongue.
In CNS, P2X4 receptors on microglia may be important in the
development of neuropathic pain.
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32. ATP IN INFLAMMATION
P2X7 receptor is widely distributed on cells of the immune
system, and ATP, apparently acting through this receptor,
causes the release from macrophages and mast cells of
cytokines .
Mice in which the receptor is deleted by genetic techniques
show a reduced capacity to develop chronic inflammation.
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33. SEROTONIN (5-HYDROXYTRYPTAMINE 5-HT)
Serotonin is produced from tryptophan and stored in vesicles in
the enterochromaffin cells of the gut and neurons of the CNS and
enteric nervous system.
 It metabolized by monoamine oxidase.
 Excess production in the body (eg, in carcinoid syndrome) can
be detected by measuring its major metabolite, 5-hydroxyindole
acetic acid (5-HIAA), in the urine.
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34. 5-HT4 Partial agonist—Tegaserod is a newer drug that acts as
an agonist in the colon.
It approved and briefly marketed for use in chronic
constipation, but because of cardiovascular toxicity, its use is
now restricted.
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37. REFERENCES
Goodman and Gilman’s The Pharmacological basis of Therapeutics 13th
edition
Essentials of Medical Pharmacology by KD Tripathi 7th edition
Basic and Clinical Pharmacology by Katzung 13th edition
Sharma and Sharma pharmacology 3rd edition
Rang and dale s pharmacology 7th E
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38. 38

39. Title Lorem Ipsum
LOREM IPSUM DOLOR SIT AMET,
CONSECTETUER ADIPISCING ELIT.
NUNC VIVERRA IMPERDIET ENIM.
FUSCE EST. VIVAMUS A TELLUS.
PELLENTESQUE HABITANT MORBI
TRISTIQUE SENECTUS ET NETUS.
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