摘要:

not available

ISSN:0008-4212    

DOI:10.1139/y85-148

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The effect of oxygen availability on theophylline metabolism by mouse hepatocytes and rat isolated livers was examined. The elimination of theophylline by mouse hepatocytes and the metabolism of theophylline to dimethyluric acid by isolated, perfused rat livers was seriously impaired when the gas mixture supplied contained less than 28% oxygen. The correlation coefficients relating oxygen supply and the concentration of theophylline remaining in mouse hepatocyte suspensions were −0.74 to −0.84. In the isolated, perfused rat liver experiments, the correlation coefficient relating oxygen availability and dimethyluric acid production was 0.87. These observations are interpreted as supporting the hypothesis that oxygen availability per se is an important factor in determining the rate of theophylline metabolism.

ISSN:0008-4212    

DOI:10.1139/y85-149

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

A novel cyclic GMP-lowering agent, LY83583(6-anilino-5,8-quinolinedkme), was used to investigate the possibility that increases in myocardial cyclic GMP levels are responsible for the negative inotropic effects of cholinergic agonists. Concentrations of carbachol from 0.3 to 3 μMelevated cyclic GMP levels in electrically paced rabbit atrial strips by 75 to 200% and decreased contractile force in the strips by 30 to 60%. Pretreatment of the muscles for 10 min with 10 μMLY83583 significantly lowered resting cyclic GMP levels and completely blocked the elevation of cyclic GMP by these concentrations of carbachol. However, the negative inotropic effects of carbachol were not blocked by the LY83583. These results indicate that the negative inotropic effects of carbachol in rabbit atrium are not mediated by increases in tissue levels of cyclic GMP.

ISSN:0008-4212    

DOI:10.1139/y85-150

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The role of anions in the maintenance of tension in electrically driven left atria isolated from guinea pigs has been examined. The disulfonic stilbene anion-channel blockers SITS (4-acetamido-4′-isothiocyanostilbene 2′-disulfonate) and DIDS (4,4′-diisothiocyano-2,2′-stilbene disulfonate) decreased the contractile force developed in a time- and concentration-dependent manner. As in the red cell anion channel, DIDS was more potent than SITS, but the maximal inhibition of tension produced byN-(4-azido-2-nitrophenyl)-2-aminoethyl sulfonate (NAP-taurine) was considerably lower than the near maximal inhibition produced by SITS and DIDS. The inhibition by SITS and DIDS was irreversible, suggesting a covalent interaction, and could not be overcome by increasing the calcium concentration or the frequency of stimulation. Consistent with a requirement for chloride anion, substitution of chloride and bicarbonate by the impermeant anion gluconate did not support contraction, while only partial tension was maintained with the lipophilic anions acetate and thiocyanate. Incubation of atria with 400 μMSITS blocked both36Cl and45Ca uptake to a similar extent, whereas the efflux of both these ions was not affected by incubation of the atria with SITS. The blockade by disulfonic stilbene anion-channel blockers of the contraction of the guinea pig myocardium may result from impairment of excitation–contraction coupling.

ISSN:0008-4212    

DOI:10.1139/y85-151

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Effects of small cardioactive peptide B on the physiology of the isolated heart and gill preparations from the molluscAplysia californicawere examined. In addition, the effects of small cardioactive peptide B and FMRFamide (Phe-Met-Arg-Phe-NH2) on adenylate cyclase activity were compared in particulate fractions of heart and gill tissues, respectively. Small cardioactive peptide B was found to exert dose-dependent, reversible changes in cardiac activity when perfused through the isolated heart. The EC50values effecting changes in heart rate and force of contraction were 3 × 10−11and 3 × 10−10 M, respectively; minimum concentrations found to effect changes in heart rate and force of contraction were normally 10−15and 10−12 M, respectively. However, some winter hearts demonstrated threshold sensitivity to small cardioactive peptide B at concentrations as low as 10−17 M. When perfused through the isolated gill, small cardioactive peptide B was found to suppress the gill withdrawal response amplitude with a threshold concentration of 10−14 Mand an EC50value of 3 × 10−11 M. Suppression of the gill withdrawal response amplitude by small cardioactive peptide B was found to be dose dependent and reversible up to a concentration of 10−9 M. At higher concentrations, the suppression tended to persist irreversibly. Small cardioactive peptide B stimulated adenylate cyclase activity in particulate fractions of both heart and gill tissues with an EC50of 0.1 and 1.0 μM, respectively. In the heart, adenylate cyclase activity increased by 32-fold at a concentration of 5 × 10−6 Msmall cardioactive peptide B. FMRFamide stimulated comparable adenylate cyclase activity in the gill only. The evidence presented suggests that small cardioactive peptide B plays an important role in the regulation of important homeostatic functions inAplysia.

ISSN:0008-4212    

DOI:10.1139/y85-152

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Diabetes results in myocardial functional alterations which are accompanied by a depression of biochemical parameters such as myosin ATPase and calcium uptake in the sarcoplasmic reticulum. Methyl palmoxirate, a fatty acid analog, is reported to decrease circulating glucose levels by inhibiting fatty acid metabolism, thus forcing carbohydrate utilization. In the present study, we attempted to prevent streptozotocin diabetes-induced myocardial alterations in the rat. Using the isolated working heart preparation, we observed a depression of myocardial function in rats 6 weeks after the induction of diabetes, which was characterized by the inability of these hearts to develop left ventricular pressures and rates of ventricular contraction and relaxation as well as control hearts at higher left atrial filling pressures. Methyl palmoxirate treatment (25 mg kg−1day−1po daily) was unable to control diabetes-induced changes in plasma glucose, triglycerides, insulin, and total lipids. Also, the functional depression seen in diabetic rat hearts was present despite the treatment. However, depression of calcium uptake and elevation of long chain acyl carnitines seen in sarcoplasmic reticulum (SR) prepared from diabetic rat hearts could be prevented by the treatment. As triiodothyronine (T3) treatment has been shown to normalize depression of cardiac myosin ATPase in diabetic rats, we repeated the study using a combination of T3(30 μg kg−1day−1sc daily) and methyl palmoxirate. While diabetic rats treated with T3alone did not show significant improvement of myocardial function when compared with untreated diabetics, the function of those treated with both T3and methyl palmoxirate was not significantly different from that in control rat hearts. These results suggest that while the combination of T3and methyl palmoxirate may have other effects which result in improved function, preventing the depression of myosin ATPase and the SR calcium uptake can account at least in part for the functional depression.

ISSN:0008-4212    

DOI:10.1139/y85-153

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The effect of sulfhydryl reagents on binding of the β-adrenergic antagonist (−)-[3H]dihydroalprenolol hydrochloride ((−)-[3H]DHA) to a microsomal fraction of rabbit ventricular muscle was studied. Incubation with the disulfide reducing agents dithiothreitol (DTT), 2-mercaptocthanol, and reduced glutathione resulted in loss of (−)-[3H]DHA binding. At 500 μMDTT, less than 50% of specific binding activity remained; at 100 mM, binding was completely eliminated. 2-Mercaptoethanol and reduced glutathione were less effective than DTT at inhibiting binding activity. The total binding capacity (Bmax) decreased from 155.4 fmol mg−1of protein, in the absence of DTT, to 92.4 and 77.5 fmol mg−1at 0.25 and 0.7 mMDTT, respectively. The equilibrium dissociation constant (KD) increased from 7.6 nM, in the absence of DTT, to 10.3 nMat 0.25 mMDTT and to 20.8 nMat 0.7 mMDTT. Thus, DTT-induced decline in (−)-[3H]DHA binding results from a decrease in both the number and affinity of membrane binding sites for the tracer. Receptors could be protected from DTT inactivation by preincubation with β-adrenergic ligands. Oxidants could not reverse inactivation, with the exception ofo-iodosobenzoate which was only partially effective. Thus, the β-adrenergic receptor of rabbit ventricular muscle contains essential disulfide moietie(s) which can be inactivated by reducing thiols.

ISSN:0008-4212    

DOI:10.1139/y85-154

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The membrane perturbational actions of pentobarbital, methohexital, and phenobarbital were analyzed in terms of their effects on the incorporation of group-specific chemical probes into protein and phospholipid structural components and on the activity of various functionally distinct ATPases in erythrocyte and brain synaptosomal membranes. When compared at concentrations producing similar degrees of antihemolysis in red cells, the three analogues differed most markedly in the nature and degree of the structural and functional alterations induced in membrane proteins, with the most highly lipophilic agent, methohexital, being frequently, although not invariably, the most potent. Comparison of the effects of pentobarbital on characteristics of trinitrobenzenesulfonic acid and 5,5′-dithiobis-(2-nitrobenzoic acid) incorporation into erythrocyte membranes with results previously obtained using other anaesthetics at concentrations producing 50% antihemolysis showed that pentobarbital behaves similarly to neutral general anaesthetics but differently from cationic local anaesthetics. Our findings suggest that the membrane perturbational characteristics of barbiturates may contribute to their diverse and complex actions on excitable tissues.

ISSN:0008-4212    

DOI:10.1139/y85-155

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Enzymatic pathways involved in the metabolism of lysophosphatidylcholine were investigated in rat heart myocardial cells. Acyl CoA-dependent acyltransferase activity was localized in microsomes, and was much greater than lysophospholipase activity in either cytosolic or microsomal fractions. The cytosolic lysophospholipase was more sensitive to inhibition by palmitylcarnitine in comparison to free fatty acids. In contrast, free fatty acids (oleate and palmitate) produced a greater inhibition of the microsomal acyltransferase and lysophospholipase than did palmitylcarnitine. A reduction in the assay pH to 6.5 resulted in an increase in microsomal acyltransferase and cytosolic lysophospholipase activities, but brought about a marked reduction in the microsomal lysophospholipase activity. At pH 6.5, the percentage inhibition of the microsomal acyltransferase by palmitylcarnitine was reduced, whereas the inhibition by palmitic acid was enhanced. The inhibition of the microsomal lysophospholipase by both palmitylcarnitine and palmitic acid was reduced at pH 6.5. With respect to myocardial ischemia, the inhibition of microsomal acyltransferase by free fatty acids and the reduction in microsomal lysophospholipase activity due to acidosis may contribute to the elevation of cellular lysophosphoglycerides which are arrhythmogenic.

ISSN:0008-4212    

DOI:10.1139/y85-156

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

A rat hepatic cytosolic [3Hjmethyltrienolone (R1881) binding protein was studied under various conditions. This protein was also compared with the male-specific high capacity – low affinity estrogen-binding protein derived from the same cytosolic fraction. Analysis of the R1881 binding protein in adult (60–85 days old) male rat liver cytosol indicated the presence of a high affinity – low capacity binding site (Kd = 0.3 nM;Bmax = 5.9 fmol/mg) and a lower affinity – higher capacity component (Kd = 10.4 nM;Bmax = 131 fmol/mg). The latter component was eliminated by addition of triamcinolone or cortisol to the assay mixture. Steroid binding to the high affinity R1881 site was specific for testosterone, dihydrotestosterone, androstenedione, and mibolerone, with a moderate specificity to cyproterone acetate, flutamide hydroxide, and estradiol. Saturation studies indicated that these steroids were binding to the same or a similar high affinity component except for flutamide hydroxide which produced nonsaturable displacement. The high affinity site had no specificity for progesterone, diethylstilbestrol, or cortisol. Like the high capacity – low affinity protein, this protein was not present in the immature, adult, or 10-day ovariectomized adult female. However, unlike the high capacity – low affinity protein, it was present in low quantities in the immature male. In addition, castration of the adult for 18 h, 4 days, or 10 days or hypophysectomy for 10–17 days did not have a significant effect on the high affinity component compared with the controls. Testosterone administration to these animals did not alter this protein binding. These studies indicate that a specific, high affinity – low capacity androgen-binding protein exists in rat hepatic cytosol. Furthermore, this protein shows age and sex dependency, but its presence is not affected by altering gonadal or hypophyseal factors in the adult male.

ISSN:0008-4212    

DOI:10.1139/y85-157

出版商:NRC Research Press    

年代:1985

数据来源: NRC