Regulation of dopamine-induced natriuresisby the dopamine-metabolizing enzyme catechol-O-methyltransferase.
Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis. A study was performed to elucidate two possible regulatory pathways of DA-induced natriuresis, i.e., metabolism and precursor delivery. This was done by use of an intraperitoneal injection of a catechol-O-methyltransferase (COMT) inhibitor, entacapone, or intravenous infusion of the DA precursor, L-dopa. Entacapone (30 mg/kg i.p.) induced a more than fivefold increase in renal sodium excretion which occurred without changes in renal haemodynamics. The natriuretic response was highly dependent on DA D(1)-like receptor activation, since the selective D(1)-like receptor antagonist SCH23390 attenuated the natriuretic response by 61%, while the selective D(2)-like receptor antagonist sulpiride was ineffective. The urinary excretion of DA did not increase. Infusion of L-dopa (60 microg/h/kg) only induced a twofold increase in sodium excretion, but the urinary excretion of DA increased more than 17-fold. The L-dopa-induced natriuretic response occurred without increments in glomerular filtration rate and could be blocked with the D(1)-like receptor antagonist SCH23390. It is concluded that the DA-metabolizing enzyme COMT is involved in the regulation of the natriuretic effect of intrarenal DA. It may be speculated that intrarenal DA activity is not primarily determined on the basis of delivered precursor, but on that of the level of DA metabolism.
Odlind
C
C
Department of Physiology, University of Uppsala, Biomedical Centre, Uppsala, Sweden.
Göransson
V
V
Reenilä
I
I
Hansell
P
P
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006706:Homeostasis; D007274:Injections, Intraperitoneal; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009570:Nitriles; D051381:Rats; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology
D001552:Benzazepines; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D017447:Receptors, Dopamine D1; D007980:Levodopa; C071192:entacapone; D002394:Catechol O-Methyltransferase; D004298:Dopamine