Dopamine-like renal and mesenteric vasodilation caused by apomorphine 6-propylnorapomorphine and 2-amino-6, 7-dihydroxy-l,2,3,4-tetrahydronaphthalene

Abstract

DOPAMINE has several unique actions in the central nervous system (CNS)—particularly the striatum—and in blood vessels, which seem to be due to interactions with specific receptors^1,2. It is not known whether the vascular and CNS effects are mediated by actions on the same or different receptors. To demonstrate receptor identity, classical receptor theory requires that tissues respond in the same rank order to a series of agonists of varying potency³. Remarkable similarities have been revealed in the relative efficacy of dopamine agonists in dilating canine renal blood vessels⁴ and in increasing dopamine-sensitive cyclic AMP accumulation in homogenates of rat striatum⁹. Further characterisation has been restricted for lack of additional agonists to extend the potency series. We describe here a comparison of the actions of two recently described dopamine agonists, 2-amino-6,7-dihydroxy-l,2,3,4-tetrahydro-naphthalene (ADTN) and 6-propyl-norapomorphine (PNA) with dopamine and apomorphine in the canine renal and mesenteric vascular beds. Apomorphine, which has structural similarities to dopamine, causes dopamine-like vasodilation⁴ and increases cyclic AMP accumulation in rat striatum⁵ but is much less potent and efficacious than dopamine in both systems. Woodruff et al.⁶ found that ADTN exerted dopamine-like actions in the CNS of mice and resembled dopamine in decreasing blood pressure in guinea pigs. ADTN is equipotent with dopamine in increasing cyclic AMP accumulation in rat striatal homogenates⁵, and intra-striatal injections of ADTN in rats and guinea pigs produce a dyskinetic phenomenon characteristic of dopamine-like agents^7,8. Cannon^9,10 suggested that PNA was a dopamine agonist on the basis of its emetic potency in the anaesthetised dog.