Absence of DA1/DA2 dopamine receptor interactions in proximal tubules of spontaneously hypertensive rats.

The impact of defective DA1 dopamine receptors in proximal tubules (PT) of the spontaneously hypertensive rat (SHR) on DA1/DA2 receptor interactions was assessed with the DA1-selective photoaffinity ligand, (+/-)-7-[125I]iodo-8-hydroxy-3-methyl-1-(4-azidophenyl)- 2,3,4,5-tetrahydro-1H-3-benzazepine ([125I]MAB). In PT membranes from both normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive rats (SHR), [125I]MAB was specifically incorporated into a polypeptide with an M(r) of 74,000 Da, corresponding to the DA1 receptor. The labeling of this band by [125I]MAB in both SHR and WKY was not prevented by SKF-82526, a potent DA1-selective agonist. However, in the presence of the DA2 antagonist, (-)-sulpiride, but not DA2 agonist, LY-171555, SKF-82526 abolished photoincorporation of [125I]MAB into the 74,000-Da band in WKY. In SHR, (-)-sulpiride failed to enhance the ability of SKF-82526 to compete with [125I]MAB for binding to the 74,000-Da subunit. In competition binding studies with SKF-82526, (-)-sulpiride induced the formation of agonist high-affinity binding sites in WKY but not in SHR. These data suggest that in membranes of SHR, but not WKY, DA1/DA2 dopamine receptor interactions are lacking.