Neurotransmitters of the non-adrenergic non-cholinergic relaxation of proximal stomach

The proximal third of the stomach (fundus plus oral corpus) relaxes during swallowing so that it can hold large amounts of food with limited increases in intraluminal pressure. This mechanism has been called "receptive relaxation" and is mediated by a vago-vagal reflex. When the food bolus reaches the stomach, gastric relaxation is maintained by another reflex starting from mechanoreceptors in the gastric wall. This second mechanism has been named "adaptive relaxation" or "gastric accommodation" and involves both intramural and vagal reflex pathways, whose inhibitory neurons are always intramural. There was initially a great deal of controversy about the identity of the neurotransmitter/s released by inhibitory neurons, but at present nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are considered to be the most likely candidates. Several lines of evidence indicate that adenosine triphosphate (ATP) might be implicated too. It seems that these neurotransmitters are co-released from the inhibitory motor neurons and are responsible for the different features of the NANC relaxation induced by low- or high-frequency neuronal firing. NO (and perhaps ATP) would be responsible for the rapid beginning and the initial rapid development of the relaxation evoked by neuronal firing at low- or high-frequency and VIP for the long duration of the relaxation evoked by high-frequency neuronal activation. This review will deal mainly with the physiological characteristics and pharmacological features of the NANC relaxation of the proximal stomach and the evidences favoring or excluding a role as inhibitory neurotransmitters of ATP, NO and VIP in different species.