Differences in photoaffinity labeling of DA1 receptors in renal proximal tubules from normotensive rat and SHR.

Renal DA1 dopamine receptors in proximal tubule membranes of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were characterized with the novel D1 dopamine receptor-selective photoaffinity probe, (+/-)-7-[125I]iodo-8-hydroxy-3-methyl-1-(4-azidophenyl)-2,3,4,5- tetrahydro-1H-3-benzazepine ([125I]MAB). Under nonphotolyzing conditions, saturation studies showed that [125I]MAB bound with similar affinity to DA1 dopamine receptors in both WKY [dissociation constant (Kd) = 16.3 nM] and SHR (Kd = 19.5 nM). At photolysis, [125I]MAB was irreversibly incorporated into a single major protein of 74,000 Da in both WKY and SHR. DA1-selective antagonists blocked photolabeling of DA1 sites with similar efficiency and specificity in SHR and WKY. However, under identical assay conditions, dopaminergic agonists were unable to block photoincorporation of [125I]MAB in SHR but not in WKY. This pattern of labeling of DA1 sites by [125I]MAB may suggest the presence of defective agonist, but not antagonist, binding domains on the receptor in SHR but not in WKY rats.