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  • Title: Diuretic effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in anesthetized rats.
    Author: Morimoto S, Matsumura Y, Ohyama T, Shinyama H, Ichihara T, Takahashi Y, Hisaki K.
    Journal: Jpn J Pharmacol; 1990 Mar; 52(3):431-9. PubMed ID: 2110272.
    Abstract:
    A synthetic amino acid, L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), can be converted to (-)-norepinephrine (NE) by aromatic L-amino acid decarboxylase (AADC) in various mammalian tissues. Recent studies have indicated the pressor and diuretic effects of L-threo-DOPS. In this study, we examined the effects of L-threo-DOPS on renal hemodynamics and function in anesthetized rats, and evaluated possible mechanisms of the diuresis. Intravenous infusion of L-threo-DOPS at 120 micrograms/kg/min exerted a significant increase in mean arterial pressure (MAP). There was a slight but nonsignificant decrease in renal blood flow (RBF). Although the glomerular filtration rate (GFR) remained at a constant level, urine flow (UF) and urinary sodium excretion (UNaV) increased significantly during the drug infusion. Pretreatment with AADC inhibitor, benserazide, completely blocked both the pressor and diuretic effects of L-threo-DOPS. When the renal perfusion pressure was protected from the pressor effect of the drug by using a Blalock clamp, the drug-induced diuresis was abolished. The diuretic effect of L-threo-DOPS was markedly attenuated by the administration of phentolamine. There was a positive correlation between plasma NE concentration and UF during the infusion of L-threo-DOPS. Intrarenal arterial infusion of L-threo-DOPS at 20 micrograms/kg/min was without effect on renal function. These results indicate that diuresis and natriuresis induced by L-threo-DOPS are dependent on the pressor effect of NE via peripheral alpha-adrenoceptor activation.
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