Roles of central glutamate, acetylcholine and CGRP receptors in gastrointestinal afferent inputs to vagal preganglionic neurones

It is unknown which neurotransmitter receptors are involved in the transfer of sensory information from the digestive tract to the brainstem. We exami ned the potential involvement of central glutamate, acetylcholine, and CGRP receptors in vagal pathways arising from gut chemo- and mechanosensitive a fferents. Unitary recordings were made from 21 vagal preganglionic efferent neurones. Neuronal discharge showed either excitation or inhibition in res ponse to oesophageal balloon distension (1-2 ml), gastric distension (40-60 mi in whole stomach or 20 mi in proximal stomach), cholecystokinin-8s (100 pmol close intra-arterially) and bradykinin (18 nmol close intra-arteriall y). Effects of glutamatergic non-NMDA, muscarinic M-1, and CGRP(1) receptor antagonism on efferent responses were investigated using CNQX (75-155 nmol i.c.v.), pirenzepine (2.5-5.0 mu mol/kg i.v.), and hCGRP(8-37) (3.2-6.4 nm ol i.c.v.), respectively. CNQX, pirenzepine, and hCGRP(8-37), respectively, altered efferent responses in 65%, 23% and 41% of neurones. When both CNQX and hCGRP(8-37) were administered, a further 58% of responses were reduced . CNQX and hCGRP(8-37) reduced a proportion of efferent responses to all st imuli whereas pirenzepine selectively reduced only efferent responses to ga stric distension. We conclude that central CGRP(1) and non-NMDA receptors a re involved in mediating a range of upper gastrointestinal mechano- and che mo-sensitive afferent inputs onto vagal efferents. M-1 receptors, on the ot her hand, are selectively involved in neurotransmission from gastric mechan oreceptors. (C) 2000 Elsevier Science B.V. All rights reserved.