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.
Vachvanichsanong
P
P
Department of Pediatrics, Georgetown University Children's Medical Center, Georgetown University, Washington, District of Columbia 20007, USA.
Sela
S
S
Sidhu
A
A
D000345:Affinity Labels; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018818:Fenoldopam / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008027:Light; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology
D000345:Affinity Labels; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D018818:Fenoldopam