Benzamide action at ?2-adrenoceptors modifies catecholamine-induced contraction and relaxation of circular smooth muscle from guinea-pig stomach

Abstract

Dopamine was shown to act on the circular smooth muscle of the stomach body to cause contraction at a yohimbine-sensitive site (alpha 2) and a relaxation at a prazosin-sensitive site (alpha 1). Metoclopramide and tiapride failed to modify either response, failed to antagonise a relaxation to phenylephrine at alpha 1 sites in the same tissue, and failed to modify the contractions caused by dopamine and phenylephrine at an alpha 1-adrenoceptor site in the pyloric sphincter. However, (+)- and (-)-sultopride and (+)-sulpiride antagonised the dopamine-induced contractions of the stomach body indicating an alpha 2-antagonist action. An ability to attenuate the relaxation of this tissue may reflect a displacement of the contraction curve to the right rather than an alpha 1-antagonist action since the response to phenylephrine was not antagonised either in this tissue or in the pyloric sphincter. Within the central nervous system the (-)-enantiomers of sultopride and sulpiride have a highly selective dopamine receptor blocking action. This contrasts with the present findings in the stomach musculature of a non-stereospecific antagonism at alpha 2-type adrenoceptors.

Pre- and Post-junctional α-Adrenoceptor-mediated Responses in the Rat Gastric Fundus In-vitro

“…We also found no evidence for post-junctional az-adrcnoceptors, either excitatory as reported in guinea-pig gastric smooth muscle (Sahyoun et al 1982). or inhibitory as reported in the guinea-pig ileum (Bauer 1982;Bauer & Kuriyama 1982).…”

“…examine these r-adrenoccptor mediated responses in the rat gastric fundus using selective a,-and a,-adrenoceptor agonists and antagonists. As r2-adrenoceptors in the gastrointestinal tract have also been reported to be present prejunctionally on non-adrenergic, non-cholinergic nerves (Fontaine et a1 1984) and post-junctionally on smooth muscle mediating contraction (Sahyoun et al 1982) or relaxation (Bauer 1982;Bauer & Kuriyama 1982), their presence at these sites in the rat gastric fundus was also investigated. Preliminary accounts of this work have previously been reported (Dettmar et a1 1984(Dettmar et a1 , 1985a(Dettmar et a1 , b, 1986.…”

In vivo and in vitro evaluation of the effects of domperidone on the gastrointestinal tract of healthy horses

“…42,43 The same experiments also revealed that higher concentrations of dopamine induced relaxation mediated by α 1 -adrenoreceptors. 42,43 In an in vitro study 45 involving horses, an α 2 -agonist (UK 14304-18) caused a significant increase in contraction amplitude, contraction frequency, and tone in jejunal longitudinal muscle strips but had no effect on jejunal circular muscle strips. Therefore, it is possible that the response to dopamine observed in longitudinal muscle strips of equine jejunum is partially mediated by action on α 2adrenoreceptors.…”

“…[39][40][41] However, in circular muscle strips from guinea pig stomachs, dopamine increases contractile activity at concentrations equivalent to those used in the present study (10 -7 to 10 -5 M). [42][43][44] The mechanism for the increased contractile activity induced by dopamine operates via α 2adrenoreceptors, given that yohimbine shifts the concentration response curve to the right. 42,43 The same experiments also revealed that higher concentrations of dopamine induced relaxation mediated by α 1 -adrenoreceptors.…”

“…[42][43][44] The mechanism for the increased contractile activity induced by dopamine operates via α 2adrenoreceptors, given that yohimbine shifts the concentration response curve to the right. 42,43 The same experiments also revealed that higher concentrations of dopamine induced relaxation mediated by α 1 -adrenoreceptors. 42,43 In an in vitro study 45 involving horses, an α 2 -agonist (UK 14304-18) caused a significant increase in contraction amplitude, contraction frequency, and tone in jejunal longitudinal muscle strips but had no effect on jejunal circular muscle strips.…”