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) 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.
Original language | English (US) |
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Pages (from-to) | 962-968 |
Number of pages | 7 |
Journal | Hypertension |
Volume | 29 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1997 |
Externally published | Yes |
Keywords
- cyclic AMP
- immunohistochemistry
- oligonucleotides, antisense
- receptors, dopamine
- renin
ASJC Scopus subject areas
- Internal Medicine