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

• Published in: Autonomic neuroscience 2000-09, Vol.83 (1), p.37-48
• Main Authors: Partosoedarso, Elita R, Blackshaw, L.Ashley
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Acetylcholine - metabolism; Action Potentials - drug effects; Action Potentials - physiology; Afferent Pathways - cytology; Afferent Pathways - physiology; Animals; Biological and medical sciences; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide - pharmacology; CGRP receptors; Digestive System - cytology; Digestive System - innervation; Digestive System Physiological Phenomena; Drug Interactions - physiology; Female; Ferret; Ferrets; Fundamental and applied biological sciences. Psychology; Glutamic Acid - metabolism; Male; Medulla Oblongata - cytology; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Miotics - pharmacology; Muscarinic receptors; Neurons, Efferent - cytology; Neurons, Efferent - drug effects; Neurons, Efferent - physiology; Non-NMDA receptors; Peptide Fragments - pharmacology; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Physical Stimulation; Pirenzepine - pharmacology; Receptors, Calcitonin Gene-Related Peptide - drug effects; Receptors, Calcitonin Gene-Related Peptide - metabolism; Receptors, Cholinergic - drug effects; Receptors, Cholinergic - metabolism; Receptors, Glutamate - drug effects; Receptors, Glutamate - metabolism; Vagal afferents; Vagal reflexes; Vagus Nerve - cytology; Vagus Nerve - drug effects; Vagus Nerve - physiology; Vertebrates: nervous system and sense organs
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/S0165-1838(00)00109-0

It is unknown which neurotransmitter receptors are involved in the transfer of sensory information from the digestive tract to the brainstem. We examined the potential involvement of central glutamate, acetylcholine, and CGRP receptors in vagal pathways arising from gut chemo- and mechanosensitive afferents. Unitary recordings were made from 21 vagal preganglionic efferent neurones. Neuronal discharge showed either excitation or inhibition in response to oesophageal balloon distension (1–2 ml), gastric distension (40–60 ml in whole stomach or 20 ml in proximal stomach), cholecystokinin-8s (100 pmol close intra-arterially) and bradykinin (18 nmol close intra-arterially). 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 μmol/kg i.v.), and hCGRP 8-37 (3.2–6.4 nmol 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 stimuli whereas pirenzepine selectively reduced only efferent responses to gastric distension. We conclude that central CGRP 1 and non-NMDA receptors are involved in mediating a range of upper gastrointestinal mechano- and chemo-sensitive afferent inputs onto vagal efferents. M 1 receptors, on the other hand, are selectively involved in neurotransmission from gastric mechanoreceptors.