Dopamine D 1A Receptors and Renin Release in Rat Juxtaglomerular Cells

Abstract

Abstract Two dopamine D 1 -like receptors have been cloned from mammals, the D 1 and D 5 receptors, also known as D 1A and D 1B receptors, respectively, in rodents. Although D 1 -like receptors are known to stimulate renin release, the receptor subtype mediating this action has not been determined. We investigated D 1 receptor subtype expression in rat juxtaglomerular cells obtained after enzymatic dispersion of kidney cortex and differential centrifugation. Juxtaglomerular cells in primary culture were immunocytochemically 85% to 95% renin positive. These cells expressed the D 1A but not the D 1B receptor (mRNA and protein). D 1 -like receptor function was demonstrated by a concentration-dependent stimulation of cAMP production by dopamine (n=5-9 per group). Fenoldopam, a D 1 -like receptor agonist, also caused a concentration-dependent increase in cAMP production and renin secretion that was blocked by the selective D 1 -like receptor antagonist SCH23390 (n=4-13 per group). Although the D 1 ligands do not distinguish between the cloned D 1 -like receptors, the actions of fenoldopam were due to occupancy of the D 1A receptor: (1) the D 1B receptor, the only other mammalian D 1 -like receptor, is not expressed in juxtaglomerular cells; (2) antisense but not sense D 1A oligonucleotides completely blocked the stimulatory effect of fenoldopam on cAMP production and renin secretion. We conclude that there is selective dopamine receptor gene expression in juxtaglomerular cells; the dopamine receptor subtype linked to the stimulation of cAMP and renin secretion in juxtaglomerular cells is the D 1A subtype.