In vivo characterization of 5‐HT_1A receptor‐mediated gastric relaxation in conscious dogs

Abstract

1 Accumulating data have been published emphasizing the important role of 5-hydroxytryptamine (5-HT) receptors in proximal stomach relaxation. However, a proper in vivo characterization of 5-HT receptors mediating gastric relaxation is still missing. In the current study, we focus on the in vivo characterization of 5-HT 1A receptors mediating relaxation of the proximal stomach in conscious dogs. 2 Beagle dogs were equipped with a gastric fistula. In the conscious state, volume changes within an intragastric bag were measured at constant pressure by means of a barostat. Results are presented as the maximum volume increase after treatment (mean7s.e.m.). All drugs were injected intravenously. 3 The 5-HT 1A receptor agonist flesinoxan (10, 50, 100 and 150 mg kg À1 ) induced a dose-dependent relaxation of the canine proximal stomach (50710, 230751, 290738 and 275733 ml, respectively; n ¼ 9 -11). The selective 5-HT 1A receptor antagonist WAY-100635 dose-dependently inhibited the flesinoxan-induced relaxation. N G -nitro-L-arginine methyl ester did not affect this relaxation, suggesting that nitrergic nerves are not involved. 4 After supradiaphragmatic vagotomy, the baseline of the intragastric volume was larger compared to that before vagotomy (317750 vs 142728 ml, respectively; n ¼ 5). Compensation for this by either reduction of the intraballoon pressure or infusion of a contractile dose of bethanechol did not establish a condition in which flesinoxan was able to relax the stomach. In contrast, nitroprusside induced a significant gastric relaxation when tone was increased by bethanechol. 5 It is concluded that flesinoxan induces proximal gastric relaxation in conscious dogs via 5-HT 1A receptors. The response is mediated through a vagal pathway without involvement of nitrergic nerves.

The influence of the novel 5‐HT1A agonist R137696 on the proximal stomach function in healthy volunteers

“…Although R137696 has a higher affinity for 5‐HT 1A receptors compared to 5‐HT 1B or 5‐HT 1D receptors, this does not exclude the possibility that it may relax the stomach by the same mechanism as sumatriptan. On the other hand, R137696 induced gastric relaxation could be mediated by a vagal pathway without the involvement of nitrergic neurons, as recently shown in dogs for the 5‐HT 1A agonist flesinoxan 19 . Finally, R137696 could act by central mechanisms.…”

The effects of acute citalopram dosing on gastric motor function and nutrient tolerance in healthy volunteers

“…Our present findings indicate that also 5‐HT release is part of this balance. Possible receptors that could decrease gastric tone are 5‐HT 1 , 5‐HT 4 and 5‐HT 7 receptors 4, 26–28 . It has been shown that the 5‐HT 4 receptor antagonist R216073 did not affect basal gastric volumes, 10 which indicates that 5‐HT 1 and/or 5‐HT 7 receptors could be more likely candidates.…”

Influence of the 5‐HT3 receptor antagonist ondansetron on gastric sensorimotor function and nutrient tolerance in healthy volunteers

“…The receptor through which 5‐HT acts in the control of the accommodation reflex therefore remains to be identified. Experiments in dogs have characterized 5‐HT 1 and 5‐HT 7 receptors that might mediate gastric relaxation 23,24 although human studies addressing this hypothesis are lacking at present.…”