Abstract

The mechanism of the inhibitory effect of dopamine on canine stomach fundus was studied in longitudinal and circular muscle fundus strips, contracted by transmural electrical stimulation or by methacholine. Results obtained for longitudinal and circular strips were similar. Dopamine (1 X 10(-6)-1 X 10(-4) M) concentration-dependently inhibited frequency-response curves to electrical stimulation; these concentrations did not change the resting tone of the strips. Dopamine (1 X 10(-4) M), tested on contractions of similar amplitude induced in the same strips by electrical stimulation at 0.5 Hz and by methacholine, inhibited the electrically induced contractions but had little influence on the contractions induced by methacholine. The inhibition of the electrically induced contractions by dopamine 1 X 10(-4) M was not influenced by the presence of cocaine 3 X 10(-5) M or hydrocortisone 3 X 10(-5) M. The alpha 1- and alpha 2-adrenoceptor antagonist phentolamine and the alpha 2-adrenoceptor antagonist rauwolscine markedly antagonized the inhibitory effect of dopamine on the response to electrical stimulation at 0.5 Hz. The alpha 1-adrenoceptor antagonist prazosin and the dopamine receptor antagonists haloperidol and domperidone had no effect. The dopamine receptor antagonist metoclopramide decreased the inhibitory effect of dopamine but had a similar effect on the inhibition caused by noradrenaline. These results indicate that the inhibitory effect of dopamine in the dog gastric fundus is mainly mediated by an interaction with alpha 2-adrenoceptors on the intramural cholinergic neurons; this effect is largely direct since it was not influenced by cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

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