A renal dopamine-1 receptor defect in two genetic models of hypertension.
Dopamine (DA), via DA-1 receptors, regulates Na+ transport in the kidneys. Dopamine is synthesized from L-DOPA in the proximal tubule and presumably secreted as an autocrine/paracrine substance to stimulate DA-1 receptors localized on proximal tubular cells. We have previously reported the presence of DA-1 receptors in renal cortical homogenates and on the isolated proximal tubule of the rat and rabbit, consistent with the dopamine autocrine/paracrine model. We have localized DA-1 receptors in the proximal straight tubule of the rabbit, and in the cortical collecting duct of the rabbit and rat, but not in the distal collecting tubule or the cortical thick ascending loop of Henle. The presence of functional DA-1 receptors has been substantiated by the coexistence of DA-1 agonist-stimulated adenylate cyclase activity in the same nephron segments in which DA-r receptors have been found. Increased concentrations of intrarenal dopamine induced by dopamine-beta-hydroxylase inhibition with SKF-102698 caused a down regulation of proximal tubular DA-1 receptors and almost complete ablation of DA-1 agonist stimulated adenylate cyclase activity. Thus, dopamine may play a role in the regulation of DA-1 receptors and their linkage with adenylate cyclase. Since alterations in the renal dopaminergic system have been measured in some forms of experimental hypertension, we studied DA-1 receptors and their coupling to adenylate cyclase in the spontaneously hypertensive rat (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)
Felder
R A
RA
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Kinoshita
S
S
Sidhu
A
A
Ohbu
K
K
Kaskel
F J
FJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology; D018818:Fenoldopam; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D011921:Rats, Inbred WKY / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012965:Sodium Chloride / Q000494:pharmacology
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D012965:Sodium Chloride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000262:Adenylyl Cyclases; D018818:Fenoldopam