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(Hypertension. 1997;29:962-968.)
© 1997 American Heart Association, Inc.

Articles

Dopamine D_1A Receptors and Renin Release in Rat Juxtaglomerular Cells

Ikuyo Yamaguchi; Lynne Yao; Hironobu Sanada; Ryoji Ozono; M. Maral Mouradian; Pedro A. Jose; Robert M. Carey; ; Robin A. Felder

From the Department of Pathology (I.Y., H.S., R.A.F.) and Department of Medicine (R.O., R.M.C.), The University of Virginia Health Sciences Center, Charlottesville; Department of Pediatrics, Georgetown University Children's Medical Center, Washington, DC (L.Y., P.A.J.); and Genetic Pharmacology Unit, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Md (M.M.M.).

Correspondence to Robin A. Felder, PhD, Department of Pathology, Box 168, MSB6171 J, The University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail raf7k{at}virginia.edu

Abstract 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 but 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.

Key Words: renin • receptors, dopamine • cyclic AMP • immunohistochemistry • oligonucleotides, antisense

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