DOPAMINE D-1A RECEPTORS AND RENIN RELEASE IN RAT JUXTAGLOMERULAR CELLS

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, respectivel y, in rodents. Although D-1-like receptors are known to stimulate reni n release, the receptor subtype mediating this action has not been det ermined. We investigated D-1 receptor subtype expression in rat juxtag lomerular cells obtained after enzymatic dispersion of kidney cortex a nd differential centrifugation. Juxtaglomerular cells in primary cultu re were immunocytochemically 85% to 95% renin positive. These cells ex pressed the D-1A but not the D-1B receptor (mRNA and protein). D-1-lik e receptor function was demonstrated by a concentration-dependent stim ulation of cAMP production by dopamine (n=5-9 per group). Fenoldopam, a D-1-like receptor agonist, also caused a concentration-dependent inc rease in cAMP production and renin secretion that was blocked by the s elective D-1-like receptor antagonist SCH23390 (n=4-13 per group). Alt hough the D-1 ligands do not distinguish between the cloned D-1-like r eceptors, 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 rec eptor, is not expressed in juxtaglomerular cells; (2) antisense but no t sense D-1A oligonucleotides completely blocked the stimulatory effec t of fenoldopam on cAMP production and renin secretion. We conclude th at there is selective dopamine receptor gene expression in juxtaglomer ular cells; the dopamine receptor subtype linked to the stimulation of cAMP and renin secretion in juxtaglomerular cells is the D-1A subtype .