## 3 Neurons and Neurochemistry of the Enteric Nervous System
The main neurotransmitter of the latter is nitric oxide (NO). In nitricic neurons, the enzyme nitric oxide synthase (NOS) is responsible for the production of NO- which is formed by the metabolism of arginine. There are three isoforms of NOS: neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Because of its short-lived free radical nature, NO is fundamentally different from classical neurotransmitters and synaptic vesicles but is delivered to the target cell as a diffusible gas, where it has no receptor in the usual sense. In the postsynaptic cell, NO directly activates the guanylate cyclase that catalyzes the synthesis of cyclic guanosine monophosphate (cGMP), which leads to an increase in the cell's cGMP levels. The proportion of nitricic neurons varies in the different stages of the intestinal tract. The nitricic neurons are essentially inhibitory motoneurons of the longitudinal muscle layer and are therefore also responsible for the inhibition of descending peristalsis via interneurons, resulting in aboral relaxation of the intestinal tract. In the enteric nervous system, neuropeptides constitute a major group of signaling molecules: neuropeptide Y (NPY) is found in both the peripheral and central nervous systems. NPY-ergic neurons are found in all layers of the intestine; some of them are extrin \begin{table}
\begin{tabular}{c c c c} \hline \hline
**\# ID** & **Neuron Type** & **Incidence** & **Neurotransmitters** \\ \hline \multicolumn{4}{c}{Myenteric neurons} \\ \hline
6 & Excitatory circular smooth muscle motor neurons & 12\% & Acetylcholine/GABA (enkephalin, tachykirins) \\ \hline
4 & Excitatory longitudinal smooth muscle motor neurons & 25\% & Acetylcholine/Calretinin (tachykirins) \\ \hline
7 & Inhibitory circular smooth muscle motor neurons & 16\% & NOS/VIP (PACAP) \\ \hline
5 & Inhibitory longitudinal smooth muscle motor neurons & \(\sim\)3\% & NOS/VIP/GABA \\ \hline
1 & Ascending interneurons (local reflex circuit) & 5\% & Acetylcholine/Calretinin (tachykirins) \\ \hline
8 & Deseending interneurons (local reflex circuit) & 5\% & Acetylcholine/NOS/VIP \\ \hline
9 & Deseending interneurons (secretomotor reflex circuit) & 3\% & Acetylcholine/Serotonin \\ \hline
10 & Deseending interneurons (migrating myoelectric complex) & 4\% & Acetylcholine/Somatostatin \\ \hline
2 & Myenteric intrinsic primary afferent neurons (IPAN) & 27\% & Acetylcholine/Calbindin (tachykirins) \\ \hline
3 & Intestinofugal neurons & 1\% & Acetylcholine/VIP (CCK, enkephalin) \\ \hline \multicolumn{4}{c}{Submucosal neurons} \\ \hline
12 & Non-cholinergic & 45\% & VIP/Galanin \\  & secretomotor/vasodilator neurons & 15\% & Acetylcholine/Calretinin \\ \hline
13 & Cholinergic secretomotor neurons & 29\% & Acetylcholine/NPY/CCK (somatostatin, CGRP) \\ \hline
14 & Cholinergic secretomotor non-vasodilator neurons & 29\% & Acetylcholine/NPY/CCK (somatostatin, CGRP) \\ \hline
11 & Submucosal intrinsic primary afferent neurons & 11\% & Acetylcholine/Calbindin (tachykirins) \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Types of neurons in the enteric nervous system with their chemical coding and proportion. sic, located mainly around blood vessels and synaptic in myenteric ganglia. The intrinsic NPY-ergic system includes motoneurons that inhibit the circular muscle layer, descending projections that modulate other neurons, and secretomotor neurons. It often co-exists as a co-transmitter with other neurotransmitters, such as NO or vasoactive intestinal peptide (VIP). Otherwise, the three NANC neurotransmitters have similar roles in the enteric nervous system: they can simultaneously affect motility, microcirculation, and secretion. Their inhibitory effects differ molecularly in that, while NO acts directly, NPY exerts its inhibitory effect on the intestinal wall smooth muscle via intrinsic cholinergic motor fibers. While VIP essentially executes the relaxation phase of the descending component of peristaltic movement, its homologue, substance P (SP), is responsible for the ascending, contractile component.