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Impairment of gastric accommodation induced by water‐avoidance stress is mediated by 5‐ HT 2B receptors
Author(s) -
Miwa H.,
Koseki J.,
Oshima T.,
Hattori T.,
Kase Y.,
Kondo T.,
Fukui H.,
Tomita T.,
Ohda Y.,
Watari J.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12775
Subject(s) - endocrinology , medicine , receptor , agonist , receptor antagonist , cyclic guanosine monophosphate , 5 ht receptor , chemistry , nitric oxide , stomach , antagonist , pharmacology , serotonin
Background Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5‐ HT 2B receptors in a guinea pig model of stress‐induced impairment of GA . Methods Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water‐avoidance stress. The role of 5‐ HT 2B receptors in impairment of GA was investigated by administering a 5‐ HT 2B receptor agonist ( BW 723C86) or antagonist ( SB 215505), the traditional Japanese medicine rikkunshito ( RKT ), a muscarinic M 3 receptor antagonist (1,1‐dimethyl‐4‐diphenylacetoxypiperidium iodide [4‐DAMP]), or a nitric oxide synthase inhibitor (N ω ‐nitro‐L‐arginine [L‐ NNA ]). Key Results In normal animals, liquid meal‐induced GA was inhibited by BW 723C86, but was not affected by SB 215505. The inhibition of GA by BW 723C86 was reversed by co‐administration of 4‐DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB 215505 and RKT significantly suppressed stress‐induced impairment of GA . After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L‐ NNA was suppressed by SB 215505 or RKT . At a dose that did not affect GA in normal animals, BW 723C86 exacerbated the impairment of GA in stressed animals. Conclusions and Inferences Stress‐induced impairment of GA may be mediated by an increased responsiveness of 5‐ HT 2B receptors, and activation of the 5‐ HT 2B receptor signaling pathway may have an inhibitory effect on nitric oxide function.