Dopamine D(1A) receptors and renin release in rat juxtaglomerular cells

Two dopamine D₁-like receptors have been cloned from mammals, the D₁ and D₅ receptors, also known as D(1A) and D(1B) receptors, respectively, in rodents. Although D₁-like receptors are known to stimulate renin release, the receptor subtype mediating this action has not been determined. We investigated D₁ 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) hut not the D(1B) receptor (mRNA and protein). D₁-like receptor function was demonstrated by a concentration-dependent stimulation of cAMP production by dopamine (n=5-9 per group). Fenoldopam, a D₁-like receptor agonist, also caused a concentration-dependent increase in cAMP production and renin secretion that was blocked by the selective D₁-like receptor antagonist SCH23390 (n=4-13 per group). Although the D₁ ligands do not distinguish between the cloned D₁-like receptors, the actions of fenoldopam were due to occupancy of the D(1A) receptor: (1) the D(1B) receptor, the only other mammalian D₁-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.