Prejunctional dopamine receptors modulate twitch responses to parasympathetic nerve stimulation in the rabbit isolated rectococcygeus muscle

Abstract

1 Field stimulation of the parasympathetic nerves supplying the rabbit isolated rectococcygeus muscle produced individual twitch responses that were inhibited by dopamine (1 × 10⁻⁸−1 × 10⁻⁵M). 2 The twitch-inhibitory effect of dopamine was reversed by haloperidol or sulpiride (1 × 10⁻⁸ − 1 × 10⁻⁵M for either) but not by phentolamine or yohimbine (up to 1 × 10⁻⁴M). Haloperidol and sulpiride were potent, specific, competitive antagonists of the twitch-inhibitory effect of dopamine; their pA₂ values were 8.39 and 7.75, respectively. In contrast, cis α-flupenthixol, fluphenazine, bulbocapnine and thioridazine were weak or inactive against dopamine. 3 Concentrations of dopamine that inhibited the twitch response to parasympathetic nerve stimulation had little or no effect on contractions elicited by carbachol or by direct muscle stimulation after abolition of neuronal conduction by tetrodotoxin. Thus, the effects of dopamine on responses elicited by parasympathetic nerve stimulation seem to be exerted at a prejunctional level rather than directly on the smooth muscle. 4 The twitch-inhibitory effect of dopamine was mimicked by epinine, N,N-diethyldopamine, N,N-di-n-propyldopamine, 5,6-ADTN, N,N-di-n-propyl 5,6-ADTN, 6,7-ADTN, apomorphine and Sandoz 27–403. Sulpiride reversed the effects of all these agonists. 5 N,N-di-n-propyl-6,7-ADTN and SK & F 82526 also inhibited the twitch response but their effects were not reversed by sulpiride. 6 SK & F 38393 and DPI had little effect on the twitch response. 7 The pharmacological characteristics of the presynaptic dopamine receptors in the rabbit rectococcygeus muscle show that they resemble those in the cat heart and rabbit ear artery in some respects but there are differences that suggest that the presynaptic dopamine receptors in the rabbit rectococcygeus muscle constitute a specific subgroup of receptors.