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Volume 17, Number 20, Issue of October 15, 1997 pp. 8009-8017
Copyright ©1997 Society for NeuroscienceSubpopulations of Gastric Myenteric Neurons Are Differentially Activated via Distinct Serotonin Receptors: Projection, Neurochemical Coding, and Functional Implications
Received March 4, 1997; revised July 31, 1997; accepted August 1, 1997.
Klaus Michel, Holger Sann, Cornelia Schaaf, and Michael Schemann Physiologisches Institut, Tierärztliche Hochschule, D-30173 Hannover, Germany
The enteric nervous system coordinates various gut functions. Functional studies suggested that neurotransmitters and neuromodulators, one of the most prominent among them being 5-HT, may act through a specific modulation of ascending and descending enteric pathways. However, it is still mostly unknown how particular components of enteric reflex circuits are controlled. This report describes experiments aimed at identifying a differential activation of enteric pathways by 5-HT. Electrophysiological and immunohistochemical methods were combined to investigate the projection pattern and the transmitter phenotype of 5-HT-sensitive gastric myenteric neurons. Of 294 intracellularly labeled neurons, 60.5% showed responses mediated via 5-HT3 receptors, 11.3% were 5-HT1P-responsive, 3.7% exhibited both 5-HT3 and 5-HT1P receptor-mediated depolarization, and 24.5% were not responding to 5-HT. The 5-HT3-responsive cells were mainly cholinergic (79%) and had ascending projections, whereas the 5-HT1P-responsive cells had primarily descending projections and were nitrergic (67%). Substance P-positive neurons were cholinergic; most of the cells (75%) exhibited 5-HT3 mediated responses and had ascending projections. Muscle strip recordings supported the functional significance of the differential location of 5-HT receptor subtypes. Thus, contractile responses of gastric circular muscle strips were dose-dependently increased by a 5-HT3 and decreased by a 5-HT1P agonist. Results indicated that excitatory ascending enteric pathways consisting of cholinergic, substance Pergic neurons were activated by 5-HT3 receptors, whereas 5-HT1P receptors were involved in activation of inhibitory descending pathways using nitrergic neurons. This suggested that different effects of 5-HT on gastric functions are related to specific activation of receptors located on different subsets of enteric neurons.
Key words: enteric nervous system; serotonin; serotonin receptors; choline acetyltransferase; nitric oxide; NADPH-diaphorase; substance P; gastric motility; stomach; guinea pig
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