Non-adrenergic non-cholinergic (NANC) transmission/mediators describes a part of the nervous system which does not use acetylcholine or noradrenaline as transmitters.

1. NON ADRENERGIC NON CHOLINERGIC
TRANSMISSION.COTRANSMISSION
PRESENTED BY
S.NIVETHA
M.PHARM -1st Semester
Department of Pharmacology

2. CONTENTS
 Neurotransmission
 Neurotransmission in ANS
 Cotransmission
 Adenosine
 ATP
 Neuropeptide Y
 Substance P
 Vasoactive intestinal peptide
 CGRP
 NO

3. INTRODUCTION
Neurotransmission:
Neurotransmission is the process in which a neurochemical signal is
transmitted from one neuron to an adjacent neuron.
Neurotransmitters are released by the presynaptic neuron, travel
across synaptic cleft, then bind to and activate the receptors on the
postsynaptic neuron.
Various neurotransmitters are:
Acetylcholine
Aminoacids (aspargine,GABA,glutamate & glycine)
Monoamines (Dopamine,histamine,epinephrine,norepinephrine)
Traces amines,purines,and variety of neuropeptides.

5. NEUROTRANSMISSION IN ANS
 Sympathetic neurotransmission:
Preganglionic neurotransmitter-Acetylcholine
Postganglionic neurotransmitter-Norepinehrine
 Parasympathetic neurotransmission:
Preganglionic neurotransmitter-Acetylcholine
Postganglionic neurotransmitter-Acetylcholine

6.  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 neurotransmitters (NANC)
often function as cotransmitter
 Smooth muscles 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 antagonist, these observations have been taken
as evidence for the existance of NANC transmission in autonomic nervous
system.

7. CO-TRANSMISSION

8.  The cotransmitter is stored in the prejunction nerve terminal along
with the primary transmitter, but in separate vesicles. However ATP is
stored in the same vesicle along with NE
 Nerve impulse releases both the transmitters concurrently.
 Acting on its own receptors, the cotransmitter modifies responsiveness
of the effector to the primary transmitter or substitutes for it
 Cotransmitter may also act on prejunctional receptors and modulate
release of the transmitters

11. In ANS besides the primary neurotransmitters Ach and NA, neurons
have been found
 Purines
ATP, Adenosine
 Peptides
Vasoactive intestinal peptide (VIP), NPY, Substance P,
enkephalins, somatostatins, CGRP, neurokinin A
 Non Peptides
Nitric oxide (NO) and prostaglandins

13. Purines
Purine nucleotides and nucleosides function as extracellular chemical
mediators subserving a wide range of functions.
Purines exert their biological actions through three families of
receptors. They are,
Adenosine receptors(A1,A2A,A2B &A3) known as P1
receptors. These are Gpcr that act through adenylyl cyclase/cAMP, or
by direct effects on Ca2+ and K+ channels.

14. P2Y metabotropic receptors (P2Y1–14), which are GPCR that
utilize either phospholipase C activation or cAMP as their signaling
system . They respond to various adenine nucleotides, generally
prefering ATP over ADP or AMP. Some also recognize pyrimidines
such as UTP.
P2X ionotropic receptors (P2X1–7) Receptor-gated cation
selective ion channels. ATP is its endogeneous ligand. Suramin
(antagonist) blocks action of ATP.

15. Adenosine as a mediator
 Simplest form of purines, adenosine is found in the biological
fluids throughout the body.
 Adenosine in tissues comes partly from this intracellular source and
partly from extracellular hydrolysis of released ATP or ADP
Adenosine in CNS
 It acts through A1 and A2 receptors. Adenosine has many
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.

16. Adenosine and Asthma
 Acting upon A1 receptor adenosine promotes mediator release from
mast cells cause enhanced mucous secretion , bronchoconstriction and
leukocyte activation
 Methylxanthines especially analogues of theophylline are adenosine
receptor antagonists
 Adenosine inhibits cardiac conduction and it is likely that all four of
the adenosine receptors are involved in this effect
Adenosine and cardiovascular system

17. Adenosine triphosphate (ATP)
 ATP exerts its action primarily through the P2X receptors. It can also
act on P2Y receptor.
 ATP is contained in synaptic vesicles of both adrenergic and
cholinergic neurons, and it accounts for many of action produced by
stimulation of autonomic nerves that are not caused by acetylcholine or
adrenaline.
 ATP is released into the neuroeffector junction , it gets metabolized by
membrane bound nucleotidases to ADP, AMP and Adenosine.
 ATP and its metabolites may also acts on presynaptic P2 receptors. So
ATP also acts as neuromodulator.

18. Neuropeptide Y
 NPY is colocalised and coreleased with NE and ATP in
sympathetic nerves especially those innervating blood vessels and
it is strong vasoconstrictor
 NPY is found in the CNS and peripheral nerves. Peripheral
administration causes positive chronotropic and inotropic effects
in the heart and hypertension.
 Direct postjunctional contractile effects by acts on Y1 subtype
receptor
 Synthesised in GABAergic neurons and acts as neurotransmitter
in cellular communication.
 Plays key role in stress, pain, anxiety, food intake, BP, and
controls epileptic seizures.

19. Vasoactive Intestinal Peptide (VIP)
 Vasoactive Intestinal Peptide (VIP) co-released with Ach
parasympathetic division of autonomic nerves system.
 VIP regulates the secretions of saliva during cholinergic
stimulation and it partly contributes in vasodialation.
 VIP may be involved in parasympathetic responses in trachea and
in the GIT tract,where it facilitate sphincter relaxation.

20. Substance P
 It is co-transmitter with acetylcholine.
 Substance P released from sensory nerves and it mediate
inflammation, it includes airway smooth muscles contraction.
 It can cause vasodilation with increased plasma exudation.
 It contraction smooth muscles binding NK2 receptor.
 Capsaicin release substance P.

21. Calcitonin gene related peptide (CGRP)
 CGRP is a potent vasodilator and useful for treating vascular
related disease.
 The receptor for CGRP is G-protein coupled receptors composed
of three functional proteins.
 It plays an important role in vascular tone regulation and involved
in migraine. It is most potent hypotensive agent .

22. Enkephalins
 Enkephalins are endogenous opioid pentapeptides that are
produced mainly by adrenal medulla and other peripheral tissues.
 It plays the role of neurotransmitter or neuromodulator of specific
neuronal systems.
 Encephalin stimulate acid secretion and inhibit pancreatic enzyme
and sodium bicarbonates from pancreas.

23. Nitric oxide
 Nitric oxide activate cGMP pathway and produces
hyperpolarization and relaxation of smooth muscles.
 Allows brain blood flow, dilates blood vessels and known as
Endothelial Dependent Relaxing Factor (EDRF)

24. REFERENCE
 Essentials of MEDICAL PHARMACOLOGY by KD Tripathi
 The pharmacological basis of Therapeutics ,Goodman and Gillman’s
 Rang and Dale’s Pharmacology