Characterization of the dopamine receptor expressed by rat glomerular mesangial cells in culture

Abstract

Incubation of cultured rat glomerular mesangial cells with dopamine caused an increasein cyclic AMP formation in a concentration-dependent manner (K a apparent 2.2 μM). The selective dopamine D 1 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 K a apparent values of 0.04 μM, 0.02 μM and 1.02 μM, 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 D 1-selective antagonist, SCH 23390, with a K i of 0.06 nM. In contrast, the D 2-selective antagonist, domperidone was four orders of magnitude less potent than SCH 23390, having a K i 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 D 1 receptor expressed by a cell line of central origin confirming that the peripheral DA 1 and the central D 1 dopamine receptor are pharmacologically similar.