[Pharmacologic characteristics of renal dopaminergic receptors: therapeutic perspectives]

The effects of dopamine (DA) on the smooth muscle fibres of the renal vascular bed are complex. They involve the postsynaptic alpha- and beta-adrenoceptors as well as the dopamine ones. On denervated kidney, in presence of alpha- and beta-blockers, intrarenal DA perfusion provokes vasodilation, increases natriuresis and stimulates renin secretion. The vasodilator effect of DA on the renal vascular bed was studied thanks to an isolated perfused rat kidney preparation which, when high concentrations of phenoxybenzamine and sotalol were present, made it possible to measure the effect of dopaminomimetics and dopaminolytics on the renal vascular resistance of a kidney previously vasoconstricted by continuous PGF2 alpha perfusion. (+)--Butaclamol and cis-flupenthixol proved to be invaluable tools to demonstrate the specificity of the dopamino-agonists response, since both shift the dose-response curve according to the criteria for competitive antagonism at doses at which their isomers are not active (fig. 2). Thus, it was possible to calculate the apparent pA2 for the various dopaminolytics and to classify them according to their affinity for the renal vascular dopamine receptors. Table 1 gives the classification. Flupenthixol, which has only a low affinity for the alpha 2-adrenoceptors, already inhibits the vasodilator effect of DA at 10(-8) M. The low stereospecificity of the enantiomers of sulpiride allows a distinction to be drawn between the "postsynaptic" vascular dopamine receptors and the presynaptic ones. The agonists of the renal vascular dopamine receptors provoked dose-dependent renal vasodilation on our preparation when phenoxybenzamine and sotalol were present and this was stereoselectively inhibited by (+)-butaclamol. Table II shows the activity of the dopaminomimetics meeting these criteria. p-Tyramine, di-propyl-m-tyramine and RU 24926 proved to have no dopaminomimetic effect. Their lack of activity seems to be attributable to the suppression of the hydroxyl in position 4. Mesenteric, splenic or cerebral artery preparations were also used to characterize the vascular dopamine receptors : tables III and IV compare the results taken from the literature. The classification obtained tallies quite well which suggests that the dopamine receptors located in the various vascular beds are identical. We compared the characteristics of the renal vascular dopamine receptor established from isolated rat kidney, with three other pharmacological models of dopamine receptor : the activation of dopamine-sensitive adenylate cyclase, the presynaptic modulation of the transmission of the sympathetic influx, and prolactin release (Table V).(ABSTRACT TRUNCATED AT 400 WORDS)