Role of neuropeptide receptor systems in vanilloid VR1 receptor-mediated gastric acid secretion in rat brain.
Previously, we reported that the injection of capsaicin into the lateral cerebroventricle (i.c.v.) stimulated gastric acid secretion via vanilloid VR1 receptors and the vagal cholinergic pathways in anesthetized rats. In the present study, we investigated the involvement of receptor systems for neurokinin A, calcitonin gene-related peptide (CGRP) and glutamate in the vanilloid VR1 receptor-mediated response. The i.c.v. injection of neurokinin A (30 nmol) stimulated gastric acid secretion in the presence of cis-2-(diphenylmethyl)-N-[(2-iodophenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine oxalate (L-703606, a tachykinin NK1 receptor antagonist, 30 nmol) and the effect was inhibited by cyclo[Gln-Trp-Phe-Gly-Leu-Met] (L-659877, a tachykinin NK2 receptor antagonist, 30 nmol); the values were 145.9 +/- 32.3 and 21.1 +/- 16.6 microEq HCl per 120 min, respectively. The value in the control group was 14.3 +/- 3.8 microEq HCl. The tachykinin NK2 receptor-mediated secretion was inhibited by i.c.v. injections of antagonists of the CGRP1 receptor (human CGRP fragment 8-37, 15 nmol) and non-N-methyl-D-aspartate (non-NMDA)-type glutamate receptor (6-cyano-7-nitroquinoxaline-2,3-dione, 10.9 nmol); the values were 30.8+/-29.8 and 5.7+/-16.9 microEq HCl, respectively. Gastric acid secretion induced by the i.c.v. injection of 30 nmol capsaicin (178.4 +/- 34.0 microEq HCl) was inhibited by antagonists of tachykinin NK2 (23.7 +/- 6.2) and CGRP1 (21.2 +/- 8.5), but not tachykinin NK1 (181.4 +/- 37.0), receptors. The gastric acid secretion induced by capsaicin was decreased by the i.c.v. pre-injection of low doses of neurokinin A or CGRP, which alone had no effect on the secretion. These findings suggest the involvement of tachykinin NK2, CGRP and non-NMDA receptor systems in the vanilloid VR1 receptor-mediated regulation of gastric acid secretion in the rat brain regions close to the lateral cerebroventricle.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
Sachie
S
Minowa
Shizuko
S
Tsuchiya
Akiyoshi
A
Someya
Syunji
S
Horie
Toshihiko
T
Murayama
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*; D011955:Receptors, Drug / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D050916:TRPV Cation Channels; D013997:Time Factors
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic; D011812:Quinuclidines; D018015:Receptors, Calcitonin Gene-Related Peptide; D011955:Receptors, Drug; D017470:Receptors, Glutamate; D018041:Receptors, Neurokinin-2; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); C076851:L 703606; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015288:Neurokinin A; D002211:Capsaicin