STEREOSELECTIVITY OF S-SULPIRIDE AND R-SULPIRIDE FOR PRESYNAPTIC AND POSTSYNAPTIC DOPAMINE-RECEPTORS IN THE CANINE KIDNEY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (1) , 67-71
Abstract
The stereoselectivity of S (S)- and R (R)-sulpiride for the pre- (prereceptor) and post (postreceptor) synaptic dopamine receptors was examined in various tissues. The effects of S and R on the pre- and postreceptor in the canine kidney were investigated. The left renal artery of pentobarbital-anesthetized dogs was exposed and mean arterial pressure and renal blood flow were monitored. Vasoconstrictor stimuli [nerve stimulation: 1-8 Hz, 2 ms, 10-20 V, 5 s; norepinephrine: 0.25-1.0 .mu.g i.a.] were produced before and during graded doses of dopamine (DA: 0.3-2.4 .mu.g/kg per min i.a.) administration. After a 15-min recovery period, vasoconstrictor stimuli were repeated before and during the reinfusion of DA at the 2.4-.mu.g/kg per min dose. While continuing DA, S or R (0.06-15.6 .mu.g/kg per min) was administered and vasoconstrictor stimuli were repeated. DA antagonized the response to nerve stimulation but not norepinephrine (P < 0.05). This effect of DA was antagonized by S at a dose of 0.12 .mu.g/kg per min but not R. S and R alone did not affect the response to nerve stimulation. In dogs pretreated with phenoxybenzamine (5 mg/kg i.a.), DA produced a decrease in renal vascular resistance (P < 0.05) and a dose of 15.6 .mu.g/kg per min of either S or R was required to block this effect of DA. S is 130 times more stereoselective for the prereceptor, whereas S and R are equipotent at the postreceptor in the canine kidney.