Synaptic Transmission at Functionally Identified Synapses in the Enteric Nervous System: Roles for Both Ionotropic and Metabotropic Receptors

Abstract

Digestion and absorption of nutrients and the secretion and reabsorption of fluid in the gastrointestinal tract are regulated by neurons of the enteric nervous system (ENS), the extensive peripheral nerve network contained within the intestinal wall. The ENS is an important physiological model for the study of neural networks since it is both complex and accessible. At least 20 different neurochemically and functionally distinct classes of enteric neurons have been identified in the guinea pig ileum. These neurons express a wide range of ionotropic and metabotropic receptors. Synaptic potentials mediated by ionotropic receptors such as the nicotinic acetylcholine receptor, P2X purinoceptors and 5-HT 3 receptors are seen in many enteric neurons. However, prominent synaptic potentials mediated by metabotropic receptors, like the P2Y 1 receptor and the NK 1 receptor, are also seen in these neurons. Studies of synaptic transmission between the different neuron classes within the enteric neural pathways have shown that both ionotropic and metabotropic synaptic potentials play major roles at distinct synapses within simple reflex pathways. However, there are still functional synapses at which no known transmitter or receptor has been identified. This review describes the identified roles for both ionotropic and metabotropic neurotransmission at functionally defined synapses within the guinea pig ileum ENS. It is concluded that metabotropic synaptic potentials act as primary transmitters at some synapses. It is suggested identification of the interactions between different synaptic potentials in the production of complex behaviours will require the use of well validated computer models of the enteric neural circuitry.

The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control

“…However, these are more difficult to investigate physiologically than other neurons, because they can only be definitively studied by direct recording techniques, even though elegant divided organ bath methods have provided insights into the properties of enteric interneurons [121]. Because of the inherent difficulties in studying the neurons, knowledge of their properties, connections and roles have been obtained from limited numbers of species and regions.…”

“…Detailed studies of synaptic connections indicate that the chains formed by two of the types of descending interneuron interconnect [125]. The ascending interneurons appear to be involved in local motility reflexes, as are two types of descending cholinergic neurons, those which contain NOS and those containing 5HT [121]. Another type of descending interneuron, the ACh/SOM interneurons, might be involved in the passage of the migrating myoelectric complexes (MMC) along the intestine.…”

Cross-inhibition between nicotinic acetylcholine receptors and P2X receptors in myenteric neurons and HEK-293 cells

“…These receptors link to protein kinase C activation, which could then alter the function of nAChRs or P2X receptors. These hypotheses would be difficult to test in cultured myenteric neurons, because nearly every neuron coexpresses P2X 2 receptors and nAChRs (37,38) and many myenteric neurons also express muscarinic and P2Y receptors (11,20). However, by using HEK-293 cells it is possible to control receptor expression.…”

Nitrergic Myenteric Neurons are Spared in Experimental Chagasic Megacolon

“…The primary neurotransmitter is Ach in the enteric excitatory muscle motor neuron [21][22][23], ascendant and descendants' interneurons [21,[24][25][26][27][28][29]. Sensitive neurons present ACh, CGRP e tachykinin as primary neurotransmitters [23,28,30,31].…”