The natriuretic response to a dopamine DA1 agonist requires endogenous activation of dopamine DA2 receptors.
Dopamine produced in the kidney acts as a natriuretic hormone by inhibiting tubular Na+,K+-ATPase activity. Previous in vitro studies have shown that Na+,K+-ATPase activity in the proximal tubule is inhibited by a synergistic action of dopamine 1 (DA1) and dopamine 2 (DA2) receptors. This in vivo study, performed on rats, investigates whether the natriuretic response to DA requires a synergistic action of DA1 and DA2 receptors. The DA1 agonist, fenoldopam, significantly increased urinary sodium excretion, but there was no increase in sodium excretion when a DA1 agonist was given together with a DA2 antagonist. Neither DA1 nor DA2 antagonists had any influence on sodium excretion. The natriuretic response to fenoldopam was also significantly attenuated after the administration of benserazide, which inhibits aromatic acid decarboxylase and thereby suppresses the endogenous production of dopamine. In conclusion, the natriuretic effect of dopamine depends on the activation of both DA1 and DA2 receptors. The DA2 receptor appears to be constitutively activated by endogenous dopamine.
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Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D018818:Fenoldopam / Q000494:pharmacology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018818:Fenoldopam