Capsaicin-sensitive extrinsic afferents are involved in acid-induced activation of distinct myenteric neurons in the rat stomach.
Challenge of the rat gastric mucosa with 0.5 mol L(-1) HCl activates nitrergic neurons in the myenteric plexus as visualized by c-Fos immunohistochemistry. In the present study, we characterized the activated neurons more extensively by their chemical coding and investigated whether a neural pathway that involves capsaicin-sensitive extrinsic afferents and/or cholinergic neurons transmitting via nicotinic receptors contributes to the activation of myenteric neurons. In multiple labelling experiments, c-Fos was examined for co-localization with nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), enkephalin (ENK), gastrin-releasing peptide (GRP), substance P (SP), calbindin D-28k (CALB) and neurofilament 145 (NF 145). All c-Fos-positive neurons were immunoreactive for NOS, VIP, NPY and NF 145, but not for SP, ENK, GRP and CALB. Nerve fibres co-expressing NOS, VIP and NPY were predominantly found in the external muscle layer and in the muscularis mucosae but rarely in the mucosa. Pre-treatment with capsaicin or hexamethonium or a combination of both pre-treatments reduced HCl-induced c-Fos expression by 54, 66 and 63%, respectively. Acid challenge of the stomach, therefore, leads to activation of presumably inhibitory motor neurons responsible for muscle relaxation. Activation of these neurons is partly mediated by capsaicin-sensitive afferents and involves ganglionic transmission via nicotinic receptors.
Schicho
R
R
Department of Experimental and Clinical Pharmacology, University of Graz, Austria. rudol.schicho@uni-graz.at
Schemann
M
M
Pabst
M A
MA
Holzer
P
P
Lippe
I T H
IT
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D005753:Gastric Mucosa / Q000294:innervation* / Q000378:metabolism; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005730:Ganglionic Blockers; D018738:Hexamethonium; D006851:Hydrochloric Acid; D002211:Capsaicin