In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 289, No. 1 ( 2005-07), p. G108-G115
Abstract:
We aimed to evaluate the gastric relaxant capacity of the 5-HT 1/7 -receptor agonist 5-carboxamidotryptamine (5-CT) in conscious dogs and to clarify the mechanism of action by use of selective antagonists, vagotomy, and in vitro experiments. A barostat enabled us to monitor the intragastric volume in response to different treatments (intravenously administered) before and after supradiaphragmatic vagotomy [results presented as the maximum volume change after treatment (mean; n = 5–11)]. In vitro experiments were performed with isolated muscle strips cut from four different stomach regions of the vagotomized dogs [results were fitted to the operational model of agonism to determine the efficacy parameter τ ( n = 5)] . 5-CT (0.5–10 μg/kg) caused a dose-dependent gastric relaxation (29–267 ml) that was completely blocked by the selective 5-HT 7 -receptor antagonist SB-269970 (50 μg/kg). After vagotomy, the relaxation to 10 μg/kg 5-CT was significantly less pronounced (73 vs. 267 ml; P 〈 0.05) but still blocked by SB-269970, whereas the response to the nitric oxide donor nitroprusside was similar to that before vagotomy (178 vs. 218 ml). In vitro, 5-CT concentration dependently inhibited the PGF 2α -contracted muscle strips before and after vagotomy. Although before and after vagotomy the response in every region was mediated by 5-HT 7 receptors (apparent affinity dissociation constant: SB-269970, 8.2–8.6 vs. 8.3–8.6, respectively), the response after vagotomy was less efficacious (log τ: 1.9 to 0.5 vs. 1.4 to −0.1). The results indicate that the 5-CT-induced proximal stomach relaxation in conscious dogs before and after vagotomy is mediated via 5-HT 7 receptors. The decreased efficacy of 5-CT in vitro after vagotomy is probably related to vagotomy-induced changes in receptor density or coupling efficiency and provides a possible explanation for the decreased in vivo response to 5-CT after vagotomy.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00012.2005
Language:
English
Publisher:
American Physiological Society
Publication Date:
2005
detail.hit.zdb_id:
1477329-6
SSG:
12
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