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 d ifferent from central nervous system (CNS) striatal D-l dopamine recep tors. In general, the renal DA-1 receptors display affinity binding va lues of dopaminergic drugs which are 6-36-fold less than those seen fo r brain D-I receptors. The renal and brain DA receptors also displayed differential sensitivity toward the alkylating agent, N-ethylmaleimid e (NEM). Inactivation of 50% of DA-1 renal receptors was achieved at l ower concentrations of NEM (5.2 mu M), relative to brain D-1 receptors (140 mu M). Western blot analyses of rat pituitary GH(4)C(1) cells, t ransfected with human CNS D-1 receptor cDNA, with human anti-D-1 dopam ine receptor antiserum, detected a single polypeptide with M-r of 66 k Da. In PTs, a specific polypeptide of higher molecular weight (M-r = 7 2 kDa) was seen. Surprisingly, in rat striatal membranes, the D-1 anti serum failed to detect any proteins within this molecular weight range . Photoaffinity labeling studies with st DA-1 selective photoligand, i dentified the identical protein by autoradiography and Western blots i n kidney, but not in striate. Together, these data indicate that renal DA-1 dopamine receptors have distinct molecular properties relative t o brain D-1 dopamine receptors. (C) 1997 Elsevier Science Ireland Ltd.