부산대학교 도서관

[gamma]-L -glutamyl-L -DOPA (gludopa) is a dopamine prodrug that is relatively specific for the kidney. Because dopamine is phosphaturic, the present study compared the phosphaturic effects of the infusion of equimolar doses of gludopa (n = 8), L -DOPA (n = 8), and [gamma]-L -glutamyl-L -tyrosine (glutyrosine, n = 6). Glutyrosine was used as a control to evaluate the effect of the glutamyl portion of gludopa on phosphate excretion. Sprague-Dawley rats (350 to 400 g) were anesthetized with 5-sec-butyl-ethyl-2-thyobarbituric acid (Inactin; 100 mg/kg, IP) and underwent thyroparathyroidectomy. Clearances were taken during the infusion of normal saline vehicle, followed by the infusion of gludopa, L -DOPA, or glutyrosine, all infused at the rate of 10 nmol/kg bolus and 0.8 nmol/kg/min (IV). To determine the contribution of glutamyl derivative to phosphate excretion, gludopa or L -DOPA was infused in the presence of SCH23390, a DA-1 receptor antagonist. Gludopa infusion significantly increased dopamine excretion (from 1.9 [+ or -] 0.2 ng/min to 17.0 [+ or -] 3.9 ng/min, [DELTA]15.0 [+ or -] 3.9 ng/min, P < .008) and fractional excretion of phosphate (from 2.6% [+ or -] 0.6% to 34.8% [+ or -] 1.8%, [DELTA]32.0% [+ or -] 1.6%, P < .001). L -DOPA infusion significantly increased dopamine excretion (from 1.4 [+ or -] 0.4 ng/min to 9.7 [+ or -] 1.6 ng/min, [DELTA]8.3 [+ or -] 1.5 ng/min, P < .001) and fractional excretion of phosphate (from 1.7% [+ or -] 0.6% to 8.2% [+ or -] 2.0%, [DELTA]6.4% [+ or -] 1.5%, P < .004). Glutyrosine infusion significantly increased fractional excretion of phosphate (from 2.8% [+ or -] 0.8% to 17.5% [+ or -] 5.2%, [DELTA]14.6% [+ or -] 4.8%, P < .03) without changing dopamine excretion ([DELTA]0.5 [+ or -] 0.2 ng/min). Infusion of gludopa in the presence of SCH23390 increased fractional excretion of phosphate (from 5.7% [+ or -] 2.5% to 12.6% [+ or -] 3.5%, [DELTA]6.8% [+ or -] 2.3%, n = 6, P < .03), whereas SCH23390 completely blocked the phosphaturic effect of L -DOPA. We conclude that [gamma]-L -glutamyl-L -DOPA is more phosphaturic than L -DOPA in the rat because of the combined effects of dopamine and the glutamyl moiety. (J Lab Clin Med 2000;135:52-6)