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

The impact of defective DA₁ dopamine recep-tors in proximal tubules (PT) of the spontaneously hypertensive rat (SHR) on DA₁/DA₂ receptor interactions was assessed with the DAi-selective photoaffinity ligand, (± )-7-[ ¹²⁵I]iodo-8hydroxy-3-methyl-l-(4-azidophenyl)-2,3,4,5-tetrahydro- ¹H-3benzazepine ([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 MT of 74,000 Da, corresponding to the DA! receptor. The labeling of this band by [¹²⁵I]MAB in both SHR and WKY was not prevented by SKF-82526, a potent DArselective 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, DAi/DA2 dopamine receptor interactions are lacking. Wistar-Kyoto rats; hypertension; fenoldopam