Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatotoxicity of CPZ was studied in the isolated perfused rat liver in order to more closely define possible mechanisms of phenothiazine-induced cholestasis. Perfusate concentrations of CPZ were increased from 5 x 10(-6) M to 5 x 10(-4) M until bile secretion was significantly inhibited. Measurements were then made of determinants of bile secretory function, including the magnitude of lobar distribution of perfusate flow, BAIF, and liver plasma membrane enzyme activity, Na+,K+-ATPase, Mg++-ATPase and 5'-nucleotidase. BAIF diminished significantly from control values of 1.76 +/- 0.07 microliter min-1gm-1 of liver to 1.34 +/- 0.15 and 0.80 +/- 0.09 following 2.5 and 5 x 10(-4) M CPZ, respectively. Perfusate flow also diminished from 5.64 +/- 0.44 to 1.24 +/- 0.12 ml min-1 gm-1 of liver 20 min following 5 x 10(-4) M CPZ and was associated with reduced flow to peripheral areas of the hepatic lobes as demonstrated by Tc-HAM. By 30 min, perfusate flow had returned to baseline values. CPZ also transiently diminished the excretion of bile acids in livers receiving a constant infusion of 40 mumol hr-1 sodium taurocholate. Defects in hepatic perfusion could not account entirely for the impairment in BAIF, since comparable mechanical restriction of perfusate flow in controls only diminished BAIF to 1.49 +/- 0.08 microliter min-1gm-1 of liver. CPZ signofocamt;u rediced tje secofoc actovotu pf Mg++-ATPase and 5'-nucleotidase but did not affect Na+,K+-ATPase in liver plasma membrane isolated 20 min after 5 x 10(-4) M CPZ. CPZ also resulted in a profound shift in the recovery of protein in isolated liver plasma membrane fractions from the light (density = 1.16) to heavier (density = 1.18) fractions. These findings, together with previous observations demonstrating alterations in hepatic ultrastructure, indicate that CPZ interacts in a complex manner with hepatocyte plasma and cytoplasmic membrane components and suggest that these drug-membrane interactions independently result in diminished hepatic perfusion, impairment of bile acid excretion, and inhibition of bile acid-independent bile secretion.
 ...
PMID:Effect of chlorpromazine on hepatic perfusion and bile secretory function in the isolated perfused rat liver. 22 76

The role of AMP and adenosine was investigated in the radiosensitization of normal brain tissues by chlorpromazine. Their metabolism was evaluated by estimating the levels of 5'-nucleotidase and adenosine deaminase activity in the brains of rats treated with chlorpromazine alone or chlorpromazine and irradiation. The extent of lipid peroxidation, measured in terms of the lipid peroxidase enzyme formed, increased with chlorpromazine treatment and irradiation. Chlorpromazine treatment was found to decrease AMP and adenosine metabolism, as shown by a marked reduction in the level of 5'-nucleotidase and ADA activity which was accompanied by a marked curtailment in the DNA, RNA and protein contents of the brain. Chlorpromazine was also found to increase the radiation-induced activity of acid phosphatase, indicating its action on the lysosomal activity of the brain cells. In the present study a low dose of chlorpromazine, i.e. 17 mg/kg body weight, was found to be more effective than a high dose of 34 mg/kg. The results of this study suggest that chlorpromazine probably sensitizes normal brain tissues to radiation by inhibiting AMP and adenosine metabolism via a hydroxy-radical induced decrease in DNA, RNA and protein metabolism with a concomitant increase in lysosomal activity.
 ...
PMID:Effect of chlorpromazine as a sensitizer of rat brain on radiation-induced AMP and adenosine metabolism. 862 92