Inhibition of 5-hydroxytryptamine-evoked autonomic transmitter release by apomorphine

Apomorphine inhibited chronotropic responses of the isolated rabbit heart to 5-HT by 40% at 1.17 micrometers and by 90% at 4.68 micrometers and strongly inhibited the outflow of 3H following preloading of hearts with [3H]- (-)-noradrenaline. Apomorphine, 4.68 micrometers, had no significant effects on transmitter release evoked by DMPP or tyramine but inhibited the responses to SNS at frequencies up to 3.2 Hz. The inhibitory effects of apomorphine on 5-HT were resistant to blockade by chlorpromazine, 1.4 micrometers, haloperidol, 1.6 micrometers, spiroperidol, 2.5 micrometers, or yohimbine, 2.8 micrometers. In contrast, the inhibitory effects of apomorphine on low frequency SNS were abolished by yohimbine. On the guinea-pig ileum treated with methysergide, apomorphine, 1.17-4.68 micrometers, blocked the indirect cholinergic responses to 5-HT less markedly than it blocked the indirect sympathomimetic responses to 5-HT on the rabbit heart. Moreover, the effects were non-selective since responses to DMPP and transmural stimulation of the intramural cholinergic nerves were similarly reduced. Modification of 5-HT receptor function is the most likely explanation for the action of apomorphine with the differential effect on 5-HT in the heart and ileum reflecting differences in the receptors and/or post receptorial events at the two sites.