Non-adrenergic and non-cholinergic transmission

Question 1

What do the terms non-adrenergic and non-cholinergic mean?

Answer 1

Acetylcholine or noradrenaline are not the only autonomic
transmitters.

Compounds are now known to function as NANC
transmitters

Question 2

What is co-transmission?

Answer 2

neurons release
more than one transmitter or
modulator each of which interacts
with specific receptors and
produces effects, often both pre- and post-synaptically

Example:
• Norepinephrine/ATP co-transmission at the sympathetic
nerve endings

Question 3

What are the advantages of co-transmission?

Answer 3

• One constituent of the cocktail (e.g. a peptide) may be removed or
inactivated more slowly than the other (e.g. a monoamine), and
therefore reach targets further from the site of release and produce
longer-lasting effects.

The balance of the transmitters released may vary under different
conditions. At sympathetic nerve terminals, for example, where
noradrenaline and NPY are stored in separate vesicles, NPY is
preferentially released at high stimulation frequencies.

Question 4

What are some examples of non-adrenergic and non-cholinergic transmitters and co-transmitters in the Peripheral nervous system?
Non-peptides

Answer 4

Non-peptides:
◦ ATP
◦ GABA
◦ 5-hydroxytryptamine
◦ Dopamine
◦ Nitric oxide

Question 5

What are some examples of non-adrenergic and non-cholinergic transmitters and co-transmitters in the Peripheral nervous system?
Peptides

Answer 5

Peptides
◦ Neuropeptide Y (NPY)
◦ Vasoactive intestinal peptide (VIP)
◦ Substance P
◦ Calcitonin gene-related peptide

Question 6

Where can NANC neurons be found?

Answer 6

The enteric system in the gut wall is the most extensively studied system containing
NANC neurons in addition to cholinergic and adrenergic fibers.

Question 7

What are some examples of transmitters in the small intestine?

Answer 7

In the small intestine, for example, these neurons contain one or more of the following:

◦ Nitric oxide synthase (which produces nitric oxide; NO),
◦ Calcitonin gene-related peptide,
◦ Cholecystokinin,
◦ Dynorphin, enkephalins,
◦ Gastrin-releasing peptide,
◦ 5-hydroxytryptamine (serotonin),
◦ Neuropeptide Y,
◦ Somatostatin,
◦ Substance P,
◦ Vasoactive intestinal peptide (VIP).

◦ Some neurons contain as many as five different transmitters.

Question 8

What is the localization and function of ATP as a NANC transmitter?

Answer 8

Extracellularly:

АТР→ ADP→ Adenosine
Adenosine, generated from the released ATP
by enzymes, acts as a modulator by causing
feedback inhibition of release of the
neurotransmitter

Purinergic receptors are classified as:
• Adenosine (P1) receptors
• ATP (P2X and P2Y) receptors
Methylxanthines (e.g. caffeine and
theophylline) preferentially block adenosine
receptors.

ADP – stimulates platelet aggregation (P2Y)
Antagonists of P2Y receptors: antiplatelet
drugs (clopidogrel, prasugrel, ticagrelor)

Location:
Postganglionic sympathetic neurons;
co-transmitter with NE.
The S nerves store ATP and NE in the same
synaptic vesicles and the 2 co-transmitters are
released together.

Function:
Fast
depolarization/contraction
of smooth muscle cells (e.g.
blood vessels, vas deferens)

Question 9

What is the localization and function of 5-hydroxytryptamine as a NANC transmitter?

Answer 9

Location:
Enteric neurons

Function:
An important transmitter or co-transmitter at excitatory
neuron-to-neuron junctions in the ENS.

Question 10

What is the localization and function of Dopamine as a NANC transmitter?

Answer 10

Location:
Some sympathetic
neurons (e.g. kidney)

Function:
Vasodilation

Question 11

What is the localization and function of Nitric Oxide as a NANC transmitter?

Answer 11

Location:
Pelvic nerves
Gastric nerves

Function:
Erection
Gastric emptying

Cholinergic nerves innervating blood vessels appear to activate the synthesis of NO by vascular endothelium.

NO causes vasodilation (NO=EDRF, endothelial-derived relaxing factor). NO is not stored, it is
synthesized on demand by nitric oxide synthase, NOS.
Drugs acting by NO: Organic nitrates

Question 12

What is the localization and function of Neuropeptide Y (NPY) as a NANC transmitter?

Answer 12

Location:

Postganglionic sympathetic
neurons;
colocalized and coreleased with
NE and ATP in most S nerves,
especially those innervating
blood vessels.

Thus, NPY, together with NE and ATP, is likely a third sympathetic co-transmitter.

Function:
Facilitates constrictor action of
NE (blood vessels). Causes long-lasting vasoconstriction.

Question 13

What is the localization and function of Vasoactive Intestinal peptide as a NANC transmitter?

Answer 13

Location:

A probable co-transmitter in
many cholinergic neurons.

VIP and Ach coexist in autonomic neurons, possibly in separate populations of storage vesicles.

Parasympathetic nerves to
salivary glands

NANC innervation of airways
smooth muscle

Function:
A vasodilator (found in many
perivascular neurons) and
cardiac stimulant.

Regulation of salivation

Bronchodilatation

Question 14

What is the localization and function of Substance P as a NANC transmitter?

Answer 14

Location:
Sympathetic ganglia;
important sensory neurotransmitter in the ENS and elsewhere.

Function:
Slow depolarization; cotransmitter with acetylcholine
Substance P is a vasodilator
(probably via release of NO).

Question 15

What is the localization and function of calcitonin gene-related peptide as a NANC transmitter?

Answer 15

Location:
e Non-myelinated sensory neurons
Present in some secretomotor
ENS neurons and interneurons

Function:
Vasodilatation; vascular leakage;
neurogenic inflammation

Question 16

What is the localization and function of enkephalin and related opioid peptides as a NANC transmitter?

Answer 16

Location:
Present in some secretomotor
and interneurons in the ENS

Function:
Appear to inhibit ACh release
and thereby inhibit peristalsis.
May stimulate secretion.