G-proteins in kidneys of spontaneously hypertensive rats.

G(s alpha)-, total G(i alpha)- and G(q/11alpha)-protein concentrations were investigated by quantitative immunoblotting in membranes of total kidney, renal cortex and medulla as well as in cortical tubules and glomeruli of Spontaneously Hypertensive Rats (SHR) and normotensive Wistar Kyoto rats (WKY), aged 5 weeks, 3 or 8 months. We found that total kidney of 5 week old SHR possess less G(s alpha)-, G(i alpha)- and G(q/11alpha)-proteins than controls. For G(s alpha)-proteins, differences found in total kidney were mirrored both in cortex (tubules and glomeruli) and in medulla.

Tachykinins contract trachea from Fischer 344 rats by interaction with a tachykinin NK1 receptor.

The contractile effect of substance P, neurokinin A, carbachol and serotonin (5-HT) on isolated Fischer 344 rat trachea was studied. Contractions of two distal tracheal rings were measured isometrically in a 2-ml organ bath. Cumulative concentration-response curves were obtained for carbachol (EC50 ring 1: 1.

Capillary gas chromatographic determination with nitrogen-phosphorus detection of the calcium antagonist nicardipine and its pyridine metabolite M-5 in plasma.

A capillary gas chromatographic method with nitrogen-phosphorus detection for the simultaneous determination of nicardipine and its pyridine metabolite M-5 was developed. The method involves extraction of the plasma with hexane-methylene chloride (1:1, v/v), followed by evaporation of the organic phase. The extract is injected into a fused-silica capillary column coated with cross-linked 5% phenyl-methylsilicone.

Metabolism and hepatotoxicity of N,N-dimethylformamide, N-hydroxymethyl-N-methylformamide, and N-methylformamide in the rat.

The metabolism and hepatotoxicity of N,N-dimethylformamide (DMF) and two of its metabolites, N-hydroxymethyl-N-methylformamide (HMMF) and N-methylformamide (NMF) were evaluated over a 4-day period in rats. DMF toxicity was dose dependent and delayed toxicity after the administration of a high DMF dose (13.7 mmol/kg) in comparison to a lower dose (4.

Influence of endotoxin on the stereoselective pharmacokinetics of oxprenolol, propranolol, and verapamil in the rat.

The influence of endotoxin-induced inflammation on the enantioselective pharmacokinetics of propranolol, oxprenolol, and verapamil, which bind to alpha 1-acid glycoprotein, was studied in the rat. The racemic mixtures were given orally. In the control animals, for propranolol and oxprenolol, the plasma concentrations of the (R)-enantiomer were higher than those of the (S)-enantiomer, while for verapamil the reverse was true.

Simultaneous determination of N,N-dimethylformamide, N-monomethylformamide and N-hydroxymethyl-N-methylformamide in rat plasma by capillary gas chromatography.

A capillary gas chromatographic method with nitrogen-phosphorus detection for the simultaneous quantitative determination of N,N-dimethylformamide, and its two metabolites, N-monomethylformamide and N-hydroxymethyl-N-methylformamide, in rat plasma has been developed. The method involves a single extraction step with ethyl acetate-acetone (4:1, v/v). The extract is injected into a fused-silica capillary column coated with Carbowax 20M.

Aging and the pharmacokinetics and metabolism of metoprolol enantiomers in the rat.

After i.v. administration of racemic metoprolol in the rat, the plasma concentrations of (R)- and (S)-metoprolol were comparable, and no differences in pharmacokinetic parameters between the two enantiomers were found.

Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients.

Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion) was developed producing plasma levels remaining above the assumed "therapeutic concentration" of 4 mg.l-1. Using the same data, it was found that a concentration of 4 mg.

Reversed-phase high-performance liquid chromatographic analysis of atenolol enantiomers in plasma after chiral derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate.

A sensitive high-performance liquid chromatographic method for the determination of the enantiomers of atenolol in rat plasma has been developed. Racemic atenolol and practolol (internal standard) were extracted from alkalinized plasma (pH 12) into dichloromethane containing 3% (v/v) heptafluoro-1-butanol, and the organic layer was evaporated. The samples were derivatized with (+)-1-(9-fluorenyl)ethyl chloroformate at pH 8.

High-performance liquid chromatographic method for the simultaneous determination of R-(-)- and S-(+)-hexobarbital in rat plasma.

The enantiospecific determination of R- and S-hexobarbital in rat plasma is described. The method involves liquid-liquid extraction of racemic hexobarbital from plasma, separation of the underivatized enantiomers by high-performance liquid chromatography on an alpha 1-acid glycoprotein column and ultraviolet detection. The mobile phase consists of a phosphate buffer (pH 5.

Determination of cetirizine in human urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of the histamine H1-receptor antagonist cetirizine in human urine was developed. Cetirizine and the internal standard are extracted from acidified (pH 5) urine (0.5 ml) into chloroform and the organic layer is evaporated to dryness.

Characterization of the beta-adrenergic transduction system in spleen mononuclear leukocyte membranes of young and senescent rats.

The effect of aging on some of the properties of the beta-adrenergic transduction system was determined in a membrane fraction of spleen mononuclear leukocytes from young (2-3 months) and old (24-25 months) rats. Receptor density was unchanged and the percentage of receptors in the high affinity configuration for isoproterenol was reduced with increasing age. Adenylate cyclase activity, either unstimulated or stimulated with forskolin, GTP or isoproterenol was not affected by aging.

The beta-adrenergic transduction system in kidneys from young and senescent rats.

beta-Adrenoceptor density, ligand affinity, high-affinity agonist binding, basal adenylate cyclase activity and cAMP synthesis upon stimulation with either forskolin, F-, guanine nucleotides (GTP or GppNHp) or isoproterenol in the presence of the nucleotides were studied in membranes prepared from kidneys of young (2-3 month) and old (24-25 month) male Wistar rats. There is a significant (P less than 0.01) 62% increase in beta-receptor density, a significant (P less than 0.

Effect of adenosine triphosphate and related purines in the rat gastric fundus.

The effect of adenosine triphosphate (ATP) and its analogues was studied in longitudinal muscle strips of the rat gastric fundus in order to characterize the purinoceptors involved. At resting tension, 10(-4) M ATP usually induced a small initial relaxation followed by a contraction; when tone was raised by administration of carbachol (10(-7) M), ATP (10(-4) M) induced a larger relaxation followed by a smaller rebound contraction. Both the contraction at resting tension and the rebound contraction were antagonized by indomethacin.

Effect of aging on properties and function of beta-adrenoceptors in rat lung.

beta-Adrenoceptor density and ligand affinity, basal adenylate cyclase activity and cAMP synthesis upon stimulation with forskolin, fluoride, guanine nucleotides (GTP or guanylyl imidodiphosphate (GppNHp) or isoproterenol in the presence of the nucleotides were studied in membranes prepared from lungs of young (aged 2-3 months) and of old (aged 24-25 months) male Wistar rats. There was a significant (P less than 0.05, 21%) increase in beta-receptor density and a significant (P less than 0.

Gradient distribution pattern of muscarinic receptors in N1E 115 mouse neuroblastoma cells.

The distribution pattern of muscarinic receptors in N1E 115 mouse neuroblastoma cells after linear and non-linear gradient centrifugation was investigated. In untreated cells, at least two forms of the receptors, with different densities, were found.

Glycan microheterogeneity of alpha 1-acid glycoprotein in sera and dialysates of patients on continuous ambulatory peritoneal dialysis.

Total concentration and concanavalin (Con A) dependent microheterogeneity of alpha 1-acid glycoprotein (AGP) were studied in sera of eight chronic renal failure patients before the start of continuous ambulatory peritoneal dialysis (CAPD), and in sera and dialysate fluids for up to 6 months of CAPD. The glycan heterogeneity of AGP in the samples was expressed as a reactivity coefficient, i.e.

Effect of turpentine-induced inflammation on the disposition kinetics of propranolol, metoprolol, and antipyrine in the rat.

Plasma concentrations after oral administration of the high extraction drug propranolol are increased in patients and animals with inflammation. This could be due to increased serum propranolol binding, but also to decreased first-pass metabolism. We studied the pharmacokinetics of 3 drugs in control rats and in rats with turpentine-induced inflammation: propranolol, which is bound extensively to alpha 1-acid glycoprotein (alpha 1-AGP); metoprolol, another high extraction drug, but which is negligibly bound to alpha 1-AGP; and antipyrine, a low extraction drug, not bound to serum proteins.

Testicular toxicity induced by single dosing of di- and mono-(2-ethylhexyl) phthalate in the rat.

The testicular toxicity of di-(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, and of its major metabolite, mono-(2-ethylhexyl) phthalate (MEHP), was assessed after a single dose in rats. Treatment with a single dose of 2.8 g/kg DEHP or 0.