DIFFERENCES IN PHOTOAFFINITY-LABELING OF DA(1) RECEPTORS IN RENAL PROXIMAL TUBULES FROM NORMOTENSIVE RAT AND SHR

Renal DA(1) dopamine receptors in proximal tubule membranes of normote nsive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) wer e characterized with the novel D-1 dopamine receptor-selective photoaf finity probe, 4-azidophenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine ([I-1 25]MAB). Under nonphotolyzing conditions, saturation studies showed th at [I-125]MAB bound with similar affinity to DA(1) dopamine receptors in both WKY [dissociation constant (K-d) = 16.3 nM] and SHR (K-d = 19. 5 nM). At photolysis, [I-125]MAB was irreversibly incorporated into a single major protein of 74,000 Da in both WKY and SHR. DA(1)-selective antagonists blocked photolabeling of DA(1) sites with similar efficie ncy and specificity in SHR and WKY. However, under identical assay con ditions, dopaminergic agonists were unable to block photoincorporation of [I-125]MAB in SHR but not in WKY. This pattern of labeling of DA(1 ) sites by [I-125]MAB may suggest the presence of defective agonist, b ut not antagonist, binding domains on the receptor in SHR but not in W KY rats.