Characterization of the dopamine receptor expressed by rat glomerular mesangial cells in culture.
Incubation of cultured rat glomerular mesangial cells with dopamine caused an increase in cyclic AMP formation in a concentration-dependent manner (Ka apparent 2.2 microM). The selective dopamine D1 receptor agonists, fenoldopam, SKF 38393 and (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) also produced concentration-dependent increases in cyclic AMP with mean Ka apparent values of 0.04 microM, 0.02 microM and 1.02 microM, respectively. Although fenoldopam and SKF 38393 were more potent than dopamine, they were partial agonists with efficacies, relative to dopamine, of approximately 60 and 35%, respectively. The dopamine analogue, 6,7-ADTN, in contrast, behaved as a full agonist. Dopamine-stimulated cAMP formation was inhibited in a concentration-dependent manner by the D1-selective antagonist, SCH 23390, with a Ki of 0.06 nM. In contrast, the D2-selective antagonist, domperidone, was four orders of magnitude less potent than SCH 23390, having a Ki of 2072 nM. In addition, SCH 23388, the stereoisomer of SCH 23390, was observed to be two orders of magnitude less potent than SCH 23390, indicating the stereoselective nature of the receptor. The potency series for the selective agonists and antagonists is the same as that described, using identical experimental conditions, for the D1 receptor expressed by a cell line of central origin confirming that the peripheral DA1 and the central D1 dopamine receptor are pharmacologically similar.
Department of Cardiovascular Studies, University of Leeds, U.K.
S E
SE
Bryson
G M
GM
Drew
A S
AS
Hall
S G
SG
Ball
A J
AJ
Balmforth
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D018818:Fenoldopam; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D013764:Tetrahydronaphthalenes; C011639:ADTN; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D018818:Fenoldopam