Mechanism of action of dopamine on the guinea-pig gastro-oesophageal junction in vitro.

1 The effect of dopamine on longitudinal muscle strips of the guinea-pig isolated gastro-oesophageal junction was compared with the response obtained to phenylephrine, isoprenaline and clonidine. Phenylephrine (5 x 10(-7) to 5 x 10(-5) M) produced a dose-related contraction, whilst dopamine (10(-6) to 10(-4) M) and isoprenaline (5 x 10(-7) to 2 x 10(-5) M) produced dose-related relaxations. Clonidine was ineffective in doses up to 10(-5) M. 5-Hydroxytryptamine (5-HT) produced a contraction. 2 Phenylephrine was antagonized by alpha 1-adrenoceptor antagonists but unaffected by beta-adrenoceptor antagonists, whilst the opposite was the case for isoprenaline. A mixture of alpha- and beta-adrenoceptor antagonists was required to inhibit completely dopamine-induced relaxations. 5-HT (3 x 10(-7) M) was specifically antagonized by methysergide (3 x 10(-6) M). 3 pA2 values for a range of alpha-adrenoceptor and dopamine receptor antagonists were determined against dopamine and phenylephrine. The relative order of potency of the antagonists was the same for both antagonists and was prazosin greater than spiroperidol greater than phentolamine greater than domperidone greater than haloperidol, with pimozide and metoclopramide being inactive. 4 Tyramine caused dose-related relaxations of the gastro-oesophageal strips which were susceptible to the same range of antagonists as dopamine. 5 Cocaine (6 x 10(-6) M) and desmethylimipramine (3 x 10(-7) M) reduced the relaxations induced by dopamine and tyramine but there were quantitative differences in the antagonism. 6 Tissue from reserpine pretreated guinea-pigs was insensitive to tyramine but the response to dopamine was only partly reduced. 7 Histological examination of the strips revealed the presence of smooth muscle but only a sparse adrenergic innervation. 8 The results suggest that dopamine acts partly indirectly and partly directly on postjunctional alpha- and beta-adrenoceptors. There is no evidence for an action on specific dopamine receptors.