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Biomedical subjects

G Powis

Publications and source records attributed to G Powis.

At least 217 records · Page 12Linked to original sources
PubMed1978

Tachyphylaxis to ethacrynic acid in the isolated atrium of guinea-pig and its relation to noradrenaline stores.

1 The isolated electrically-paced atrium of the guinea-pig developed a dose-dependent increase in the force of contraction in response to ethacrynic acid (12-100 microgram/ml) which was blocked by pretreatment of the animals with reserpine but was unaffected by desipramine or colchicine added to the bathing medium. 2 There was a rapidly developing tachyphylaxis to repeated doses of ethacrynic acid which was not reversed by rest or incubation of the tissue with noradrenaline. 3 There was no cross tachyphylaxis between ethacrynic acid and tyramine, amphetamine or nicotine. 4 Ethacrynic acid (200 microgram/ml) decreased the noradrenaline content of the atria by 32%. 5 It is concluded that ethacrynic acid exerts its effects indirectly through the release of endogenous noradrenaline and that the mechanism of release seems to be different from that of other known indirect sympathomimetic drugs.

Animals↗
PubMed1978

The effects of exercise and adrenaline infusion upon the blood levels of propranolol and antipyrine in the horse.

There are now several examples showing that experimentally induced changes in hepatic blood flow can have a marked effect upon the elimination of certain high clearance drugs. Changes in hepatic blood flow produced by exercise might therefore be expected to influence the clearance of these drugs. There was an increase of up to 100%, compound to control values, in the plasma levels of propranolol in horses given either d- or dl-propranolol, 0.2 mg/kg b.wt., and then subjected to sustained exercise for 30 minutes. There was, however, no similar increase with exercise in the plasma levels of antipyrine in horses given antipyrine, 50 mg/kg b.wt. Intravenous infusions of adrenaline, 1 microgram/kg b.wt./min for 10 minutes also produced an increase of about 70% in the plasma levels of d-propranolol.

Animals↗
PubMed1977

Calorimetric study of microsomal membrane.

Differential scanning calorimetric measurements of normal rat liver microsomes reveal a single thermal transition at about 50 degrees. This transition is assigned to irreversible prorein denaturation. There is no evidence for a reversible lipid phase transition at any temperature above 0 degrees, indicating that the microsomal membrane is in teh fluid state under these conditions. Rats fed a fat-free diet which increases the degree of saturation of fatty acids in the membrane lipids do produce microsomal membranes exhibiting a reversible lipid phase transition. The NADH=dependent and NADPH-dependent enzymatic reductions of cytochrome c show linear Arrhenius behavior in the normal rat liver microsomes but reveal discontinuities and breaks in the Arrhenius plots at approximately the calorimetrically determined phase transition temperatures in microsomes from rats fed the fat-free diet. Hence, the fluidity of cell membranes can be altered by diet with consequent effects on membrane-supported functions. The data further show that the lipid organization of the membrane is not independent of the protein component and supports models of membrane structure where a separate class of lipids forms a boundary between the bulk phase and the proteins.

Animals↗
PubMed1976

The metabolism and binding of catecholamines by the hepatic microsomal mixed-function oxidase of the rat.

Noradrenaline and adrenaline were metabolized by an NADPH- and oxygen-dependent process located within the hepatic microsomal fraction of the rat. Metabolism was inhibited by CO and compound SKF 525A, but not by pargyline, an inhibitor of monoamine oxidase, or by 3,4-dimethoxy-5-hydroxybenzoic acid, an inhibitor of catechol O-methyltransferase. It is concluded that the enzyme system responsible for the metabolism of the catecholamines was the microsomal mixed-function oxidase. The Km for noradrenaline was 2.4 mM and for adrenaline 1.0 mM, and V 15.6 and 3.6 nmol/min per mg of microsomal protein respectively. Both catecholamines bound to the microsomal fraction, producing a type II spectral change, with a Ks for noradrenaline of 0.9 mM and for adrenaline of 1.0 mM, and showed other characteristics of type II compounds by inhibited the reduction of cytochrome P-450 by NADPH and exhibiting an enhanced metabolism in the presence of acetone. The major product of catecholamine metabolism was an as yet unidentified alkali-labile compound, which did not correspond to any of the recognized catecholamine metabolites.

Animals↗
PubMed1976

Development of liver microsomal oxidations in the chick.

1. Liver microsomal preparations from chick embryos (1 day before hatching) and from 1-7 day old chicks were assayed for oxidative drug-metabolizing activity with aminopyrine, aniline and naphthalene as substrates. 2. Activities for all three substrates were highest in preparations from 1 day-old chicks. These were more than twice as active as the 7 day-old preparations and about three times as active as those from the embryos. 3. The increase in drug-metabolizing activities in newly-hatched chicks was the same for either sex and persisted for 3 days before declining towards the 7 day-old levels. 4. The developmental time-course fo the liver microsomal drug-metabolizing activities was independent of any factor in the 105 000 g supernatant fractions and of such microsomal parameters as cytochrome b5 and cytochrome P-450 content, and NADPH-cytochrome c reductase activity, but was related to changes in NADPH-cytochrome P-450 reductase levels. 5. Treatment of 7 day-old chicks with exogenous inducers, 3-methylcholanthrene or phenobarbital sodium (100 mg/kg, intraperitoneally) brought about maximal stimulation of microsomal activity as 18-24 h. The time-course of this induction was reflected by changes in microsomal cytochrome P-450 content and NADPH-cytochrome P=450 reductase activities. 6. Some induction of liver microsomal drug metabolism in 7 day-old chicks could also be brought about by injecting certain lipid-soluble egg yolk extracts.

Aging↗
PubMed1975

Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat.

Methanol and ethanol administered to rats as a single oral dose increased aniline hydroxylation by the hepatic microsomal fraction by a maximum of 169 and 66% respectively, whereas aminopyrine demethylation was inhibited by 51 and 61%. The concentration of microsomal cytochrome P-450, and the activities of NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were unchanged. Propan-2-ol, administered as a single oral dose, increased microsomal aniline hydroxylation by 165% and increased aminopyrine demethylation by 83%. The concentration of cytochrome P-450 was unchanged whereas NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were both increased by 38%. Methanol, ethanol and propan-2-ol administration resulted in a decreased type I spectral change but had no effect on the reverse type I spectral change. Methanol administration decreased the type II spectral change whereas ethanol and propan-2-ol had no effect. Cycloheximide blocked the increases in aniline hydroxylation and aminopyrine demethylation but could not completely prevent the decreases in aminopyrine demethylation. The increases in aniline hydroxylation were due to an increase in V, but Km was unchanged. The ability of acetone to enhance and compound SKF 525A to inhibit microsomal aniline hydroxylation was decreased by the administration of all three alcohols. The decrease in the metabolism of aminopyrine may result from a decrease in the binding to the type I site with a consequent failure of aminopyrine to stimulate the reduction of cytochrome P-450. Methanol administration may lead to an increase in aniline hydroxylation because of a failure of aniline to inhibit cytochrome P-450 reduction.

1-Propanol↗