The absorption, distribution, and excretion in mice of a quinolinemethanol antimalarial, 2,8-bis(trifluoromethyl)-4-(1-hydroxy-3-(N-t-butylamino)propyl)quinoline phosphate (WR 184,806).

Approximately 75% of the radioactivity derived from WR 184806-14C was excreted in the feces with the remainder in the urine after po administration. At least 77-85% of the dose was absorbed by 2-8 hr; lungs, liver, skeletal muscle, kidneys, small intestine (less contents) and residual carcass were major sites of deposition of total radioactivity. Within these tissues the radioactivity present was predominantly as WR 184,806 rather than its metabolites. Peak blood plasma levels of WR 184,806 occurred at 2-4 and 7-10 hr. The peak erythrocyte level of WR 184,806 occurred at 6 hr. The presence in the urine and feces of unchanged WR 184,806 was confirmed by thin-layer chromatography and inverse isotope dilution.

Hepatic dopamine sulfotransferases in untreated rats and in rats subjected to endocrine or hypertension-related treatments.

Here we describe the dopamine sulfotransferase activity of rat liver cytosol. With cytosol, 3'-phosphoadenosine-5'-phosphosulfate and dopamine Km values were 17.2 +/- 4.1 and 22.4 +/- 3.5 microM. Females possessed 23 to 37% of dopamine sulfotransferase levels, per gm liver, in males. DEAE-Sephadex A-50 chromatography resolved dopamine sulfotransferase activity to dopamine sulfotransferase I and dopamine sulfotransferase II. Dopamine sulfotransferase II comprised 79 +/- 10 or 61 +/- 18% of dopamine sulfotransferase in males or females in routine assays. 4-Methoxytyramine gave 609 or 179% of mean dopamine sulfotransferase activity with dopamine sulfotransferase I or II. Dopamine and 3-methoxytyramine were comparable substrates. Epinephrine was less effective. Mn++, Cd++, Zn++, Na+ and K+ inhibited dopamine sulfotransferase II. Mg++ activated it. Dopamine sulfotransferase II from males was purified 184 +/- 64-fold. Its Km values for 3'-phosphoadenosine-5'-phosphosulfate and dopamine were 12.7 +/- 1.5 and 47.5 +/- 6.7 microM, respectively. Its dopamine sulfotransferase mechanism was sequential. The molecular weight of dopamine sulfotransferase II was 49,100 +/- 4,000 by Sephadex G-100 chromatography. Dopamine sulfotransferase II preferred phenol to catecholamines. Dopamine and 3,4-dihydroxybenzylamine were its best catecholamine substrates. Adrenalectomy or castration of males led to 35 or 45% mean decreases of dopamine sulfotransferase levels, indicating adrenal and gonadal participation in control of dopamine sulfotransferase production. Testosterone had no effect in either sex, whereas estradiol led to 40% mean decreases of dopamine sulfotransferase levels in males. This suggested a role for ovaries in dopamine sulfotransferase production, supported by 55 to 102% increased dopamine sulfotransferase levels after ovariectomy. Okamoto-hypertensive males or males given hypertensogenic doses of cortisol exhibited 37 or 48% mean increases of dopamine sulfotransferase levels per gm liver. Antihypertensive spironolactone or hydralazine led to 30% mean decreases of dopamine sulfotransferase levels. Altered dopamine sulfotransferase levels after all experimental manipulations were due mostly to changed dopamine sulfotransferase II content. Dopamine sulfotransferase II is compared to other reported enzymes that sulfate catecholamines.