Search results for "RATS"

Strategies and Molecular Probes to Investigate the Role of Cytochrome P450 in Drug Metabolism

2003

Drug metabolism is the major determinant of drug clearance and, because of polymorphic or inducible expression of drug-metabolising cytochrome P450s (CYPs), is the factor most frequently responsible for interindividual differences in pharmacokinetics. A number of well characterised CYP substrates and inhibitors have been identified that allow precise measurements of individual CYP isoforms. Their use, alone or in combination, facilitates the phenotype characterisation of hepatocytes in vitro and in vivo. Two procedures are used for in vitro investigation of the metabolic profile of a drug: incubation with microsomes and incubation with metabolically competent cells. The major limitation of …

P1 and P2 receptors in the rat duodenal smooth muscle

1989

Modifications induced in the renin-angiotensin-aldo-sterone system of rats by alpha-blocking drugs.

1978

Summary The data reported in the present paper refer to quantitative variations of plasma renin activity and plasma aldosterone levels after administration of alpha-blocking agents, i.e. phentolamine, phenoxybenzamine and gihydroergotoxin derivatives, either to rats kept on a standard diet with water ad libitum or to rats receiving distilled water load, the latter treatment causing an increase of both plasma renin activity and plasma aldosterone levels if compared to control values. No strict correlation between (a) drug-induced modifications of plasma renin activity and plasma aldosterone levels and (b) blood pressure drop caused by the same drugs was shown to occur under either experiment…

Effect of nutritional imbalances on cytochrome P-450 isozymes in rat liver

1988

Male Sprague-Dawley rats were fed for six weeks either a control diet containing 22% casein (C) and 5% fat (F) or a low-protein diet (6% C, 5% F) or high-lipid diet (30% C, 30% F). A group of rats received a control diet containing 50 ppm of Phenoclor DP6. Three major forms of cytochrome P-450, UT 50, BP 3a and MC 2 were purified from livers of DP6-fed rats and only two forms, UT 50 and PB 3a, were purified from control and dietary groups. The amino acid composition and the catalytic activities towards all substrates tested were only significantly modified in the purified UT 50 P-450 isozyme from rats fed the low-protein diet. The N-terminal sequence analysis shows that cytochrome P-450 UT …

Calcium dependence of the evoked arginine vasopressin release by electrical stimulation and by L-glutamate.

1989

In vitro incorporation of amino acids into proteins stimulated by RNA from unfertilized sea urchin eggs.

1964

Temperature dependence of the toxic effects of phenytoin on peripheral neuromuscular function of the rat tail.

1990

We studied the acute effects of a single dose of phenytoin (250 mg/kg) on peripheral neuromuscular function. The evoked muscle action potentials of the dorsal segmental muscles in the rat tail, and the conduction velocity of the dorsal nerve trunk which innervates them, were measured before and after the intraperitoneal injection of phenytoin. The experiments were performed at different temperatures, 27 (physiological tail temperature), 36 and 37 degrees C (physiological central temperature) in different groups of animals. The amplitudes of the evoked muscle action potentials in the treated groups showed no significant modifications at 27 degrees C, at 36 degrees C a small nonsignificant de…

Prevention of the acute neurotoxic effects of phenytoin on rat peripheral nerve by H7, an inhibitor of protein kinase C.

1992

Abstract The neurotoxic effects of a single dose of phenytoin (150 mg/kg body weight) alone or 30 min after H7 (a protein kinase C inhibitor) injection (20 mg/kg body weight) were investigated in terms of peripheral neuromuscular function and Na + ,K + -ATPase activity of the sciatic nerve. This intraperitoneal injection of phenytoin induced complete blockade of muscle action potentials in the dorsal segmental muscles of the rat tail evoked by electric stimulation of the caudal nerve and a 40% decrease in the Na + ,K + -ATPase activity of the rat sciatic nerve when compared with control values, measured as the difference between total and ouabain-insensitive ATPase activity. Prior administr…

Influence of peroxisome proliferators on phosphoprotein levels in human and rat hepatic-derived cell lines.

1995

To elucidate the effect of peroxisome proliferators on the signal-transduction pathway, we have compared the effect of ciprofibrate, an hypolipaemic agent, on the overall phosphoprotein level between rat and human well differentiated hepatic derived cell lines. The phosphorylation status of several phosphoproteins in the rat Fao cell line was increased by the drug while no changes were observed in the human HepG2 cell line. In rat Fao cells, this increase, which is concentration and time dependent, can be as much as eightfold for 20-kDa and 22-kDa proteins. Wy-14,643, a non-fibrate molecule and a more potent peroxisome proliferator than ciprofibrate, increased the phosphorylation status of …

Modulation of neuronal phospholipase D activity under depolarizing conditions

1999

Neuronal phospholipase D (PLD) activity was hypothesized to be involved in vesicle trafficking and endocytosis and, possibly, transmitter release. We here report that prolonged depolarization of rat hippocampal slices by potassium chloride (KCl) or 4-aminopyridine inhibited PLD activity. Similarly, PLD activity in rat cortical synaptosomes was significantly inhibited by depolarizing agents including veratridine and ouabain. Inhibition of calcium/calmodulin kinase II (CaMKII) which positively modulates synaptosomal PLD activity [Sarri et al. (1998) FEBS Lett. 440, 287-290] by KN-62 caused a further reduction of PLD activity in depolarized synaptosomes. Depolarization-induced inhibition of PL…