C001: Differential expression and regulation of dopamine-1(d1) and dopamine-5(d-5) receptor function in human kidney

• Published in: American journal of hypertension Vol. 13; no. S2; p. 156A
• Main Authors: Sanada, H., Xu, J., Watanabe, H., Jose, P.A., Felder, R.A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2000
• Subjects: cAMP; Dopamine; dopamine receptor
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(00)00649-X

The renal dopaminergic system plays an important role in the regulation of blood pressure, sodium balance, and kidney function. Two D1-like receptors (D1 and D5) are expressed in mammalian kidney, however, their distribution and cAMP linkage in human kidney have not been studied. With immunohistochemistry, we found that the D1 receptor is expressed in luminal and basolateral membrane of proximal tubules (PT), distal convoluted tubules (DCT), loop of Henle (LH), cortical collecting duct (CCD), juxtaglomerular apparatus (JGA), and intima and smooth muscles of renal arterioles. The D5 receptor, like the D1 receptors, is found in proximal tubules but only in luminal membrane. The D5 receptor, unlike the D1 receptor, is not found in the other nephron segments or arterioles. Neither the D1 nor D5 receptors to D1-like agonist stimulation of cAMP production, in proximal tubules in culture. We studied the effect of dopamine and fenoldopam, a D1-like agonist, in the presence or absence of sense or antisense oligonucleotides, since no ligand can distinguish the D1 from the D5 receptor. Basal cAMP production was 1107 ± 22 fmol/mg protein/min (n = 8). Dopamine and D1-like agonist, fenoldopam (10−9–10−4) dose-dependently increased cAMP production, Emax = 32 ± 3% and 67 ± 1% respectively, D1 antisense oligonucleotides decreased the ability of fenoldopam (10−6 M) to increase cAMP production (−76 ± 5%, p < 0.05, n = 6). In contrast, D5 antisense oligonucleotides had little effect (−15 ± 5%, n = 4). Sense or scrambled oligonucleotides D1 and D5 had neglible effect of cAMP production. We conclude that D1 and D5 receptors are differentially expressed in the human kidney. In renal proximal tubules where both D1-liked receptors are expressed, D1 receptor predominates over D5 receptors action on cAMP production.