Molecular and structural differences between rat brain D-1 and renal DA-1 dopamine receptors.
Renal DA-1 dopamine receptors in proximal tubules (PTs) of the Wistar-Kyoto (WKY) rat display pharmacological binding properties which are different from central nervous system (CNS) striatal D-1 dopamine receptors. In general, the renal DA-1 receptors display affinity binding values of dopaminergic drugs which are 6-36-fold less than those seen for brain D-1 receptors. The renal and brain DA receptors also displayed differential sensitivity toward the alkylating agent, N-ethylmaleimide (NEM). Inactivation of 50% of DA-1 renal receptors was achieved at lower concentrations of NEM (5.2 microM), relative to brain D-1 receptors (140 microM). Western blot analyses of rat pituitary GH4C1 cells, transfected with human CNS D-1 receptor cDNA, with human anti-D-1 dopamine receptor antiserum, detected a single polypeptide with M(r) of 66 kDa. In PTs, a specific polypeptide of higher molecular weight (M(r) = 72 kDa) was seen. Surprisingly, in rat striatal membranes, the D-1 antiserum failed to detect any proteins within this molecular weight range. Photoaffinity labeling studies with a DA-1 selective photoligand, identified the identical protein by autoradiography and Western blots in kidney, but not in striate. Together, these data indicate that renal DA-1 dopamine receptors have distinct molecular properties relative to brain D-1 dopamine receptors.
Sidhu
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Department of Pediatrics, Georgetown University Medical Center, Georgetown University, Washington DC 20007, USA. sidhua@odrge.odr.georgetown. edu
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Sela
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White
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Kimura
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Patel
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D000818:Animals; D001552:Benzazepines / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D001552:Benzazepines; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D017447:Receptors, Dopamine D1; D005033:Ethylmaleimide