摘要:

The effect of ciclosporin (CS) on hepatic and renal glutathione was investigated in 36 male Sprague-Dawley rats weighing 200–250 g each. CS (120 µg/kg/day, i.p.) treatment caused a significant decrease in both hepatic and renal glutathione content. The rat hepatic glutathione levels decreased by 16 % within 1 h of a single CS treatment and continued decreasing to 50% following chronic treatment with CS for 7 days. Renal glutathione content decreased only marginally (3%) within 1 h of CS treatment. However, it decreased by 17% within 24 h and continued to decrease during the 7 days of chronic treatment. This decrease in the content of both hepatic and renal glutathione may contribute to the toxicity observed during treatment with

ISSN:0031-7012    

DOI:10.1159/000138599

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Binding of cefpiramide (CPM) and other β-lactam antimicrobial agents to 2(3)-tert-butyl-4-hydroxyanisole (BHA)-induced liver glutathione (GSH) S-transferases (EC 2.5.1.18) from CD-I mice was studied. A marked induction of hepatic GSH S-transferase from mice fed BHA was observed. Gel chromatography of liver cytosol from mice fed BHA showed an increased binding of CPM, cefotetan and cefazolin to BHA-induced GSH S-transferases. The extent of their binding to GSH S-transferase seemed to be correlated with the extent of their excretion into the bile. Binding of CPM to the GSH S-transferase fraction was inhibited by both indocyanine green, which is known to bind liver GSH S-transferases intensively, and by cefoperazon, which is mainly excreted into the bile. This study suggests that GSH S-transferases are the main binding proteins of CPM in the liver cytosol fraction and play an important role as carrier proteins of CPM and some antimicrobial agents in mouse liver

ISSN:0031-7012    

DOI:10.1159/000138600

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The effects of tin-protoporphyrin (SnPP) on the activity of heme oxygenase in the epithelium of the proximal region of the small intestine were examined in male Sprague-Dawley rats. A single dose of SnPP (25 µmol/kg body weight) administered either parenterally or by gavage-produced time-dependent decreases in the activity of microsomal heme oxygenase over 24–48 h. Although heme oxygenase activity reverted to normal levels within 24 h after oral dosing, parenteral treatment resulted in substantial (70%) inhibition of the enzyme through at least 48 h after administration of the metalloporphyrin. In vitro, SnPP was shown to be a competitive inhibitor of microsomal heme oxygenase (Ki = 0.017 µM). Tissue tin levels were determined by graphite furnace atomic absorption spectroscopy 48 h after SnPP treatments. Comparable levels of tin were found in the liver and kidney after parenteral treatment (14.34 ± 1.50 and 14.39 ± 0.45 µg/g dry weight, respectively) while only 1.5–3% of these amounts were found in these organs after oral treatment with the metalloporphyrin. These studies establish that the rate-limiting enzyme in the catabolism of heme to bilirubin is inhibited in intestinal epithelium to the same extent as the enzyme is inhibited in othe

ISSN:0031-7012    

DOI:10.1159/000138601

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The purpose of this study was to compare the effects of amiloride, an inhibitor of Na+-H+ exchange, and its analog 3’,4’-dichlorobenzamil, a more specific inhibitor of Na+-Ca2+ exchange on the response of cardiac myocytes to ouabain. Cardiac myocyte aggregates were prepared from myocytes obtained from 7-day-old chick embryo hearts. Ouabain at 10–6M produced a marked and significant (p < 0.05) reduction in contractile frequency. Amiloride, at 10–7 to 10”5 M produced a definite, significant (p < 0.05) and dose-dependent reduction in this effect of ouabain. In contrast, dichlorobenzamil, 10–7 to 10–6M, significantly (p < 0.05) accentuated this effect of ouabain. Thus, amiloride and its analog dichlorobenzamil have different effects on the cardiac responses to ouabain presumably because of the differences in the specificity of their inhibition of Na+/H+ and Na+/Ca2+ exchange. Thus to the extent that the effects of amiloride and dichlorobenzamil are mediated through, respectively Na+-H+ and Na+-Ca2+ exchange, these data suggest that ouabain-induced reduction in contractile frequency is mediated through Na+-H+ exchange while Na+-Ca2+ exchange acts to minimize this action of ouabain. Amiloride may be useful to oppose the negative chronotropic effect of ouabain while dichlorobenzamil accentuates this effe

ISSN:0031-7012    

DOI:10.1159/000138602

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138603

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The effects of 3 α2-adrenergic receptor agonists on renal function in vasopressin (AVP)-deficient Brattleboro (DI) rats were evaluated. The aim of this study was to determine the relative contribution of central versus peripheral α2- adrenoceptors in mediating diuresis and natriuresis, as well as the role of α2-adrenoceptors in antagonizing the actions of AVP. In addition to the studies of renal function, the effects of AVP deficiency on renal α2-adrenoceptor affinity and number was evalauted along with determination of peripheral catecholamine stores. The centrally acting α2-adrenergic agonists guanabenz and guanfacine significantly increased urine output and sodium excretion in Long-Evans (LE) rats. Guanabenz and guanfacine increased urine output in DI rats but failed to increase sodium excretion. The polar α2-adrenergic agonist, ST-91, increased sodium excretion in both LE and DI rats, however, at a dose of 1.0 mg/kg urine output was significantly decreased in DI rats. The 3 α2-adrenergic agonists increased potassium excretion in LE rats, but at the 1.0-mg/kg dose of guanabenz and ST-91, potassium excretion was significantly inhibited in DI rats. Renal α2-adrenergic receptors and norepinephrine stores were not altered in DI rats. Adrenal NE stores were significantly elevated in DI rats relative to LE rats. The results of this study suggest that in the absence of AVP, centrally acting α2-adrenergic agonists have limited natriuretic action, although peripheral activation of α2-adrenoceptors is sufficient to elicit natriuresis irrespective of the presence of AVP. The chronic deficiency of AVP does not alter renal α2-adrenergic receptor number, but the natriuretic and kaliuretic actions of α2-adrenergic agonists are altered

ISSN:0031-7012    

DOI:10.1159/000138604

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

We have investigated the presence of M1-subtype muscarinic receptors on pulmonary vascular endothelium in vivo. Utilizing multiple indicator-dilution techniques, we studied [3H]-pirenzepine ([3H]-PNZ; a selective M1 receptor antagonist) binding during a single transpulmonary pass in anesthetized, artificially ventilated rabbits, before and after administration of 4.3 µmol/kg of the nonselective muscarinic receptor antagonist atropine. [14C]-Dextran (MW = 70,000–90,000) served as the intravascular indicator. Before atropine administration, approximately 20% of [3H]-PNZ was lost (i.e., presumed bound to PNZ-specific and nonspecific sites) during a single pass through the pulmonary microvasculature. A significant decrease in [3H]-PNZ binding occurred 90 min after atropine (to approximately 60% of total initial binding), but not after saline, reflecting the loss of specific binding to M1 receptors. These data are in support of previous findings from our laboratory indicating a pressor response to M1 receptor stimulation in the rabbit pulmonary circulation as well as an endothelium-dependent contractile response to M1 receptor stimulation in vit

ISSN:0031-7012    

DOI:10.1159/000138605

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The present studies were desgined to examine the effect of local anesthetics (benzyl alcohol, lidocaine, and procainamide) on the secretory response of parietal cells to histamine, dbcAMP, and carbachol. Studies were performed in vitro using isolated cells from rat stomachs, and acid production was determined by 14C-aminopyrine accumulation. In addition, the (H+-K+)-ATPase activity of microsomal vesicles isolated from parietal cells was determined. Lower concentrations of the drugs studied increased the basal aminopyrine accumulation and potentiated the secretory response of parietal cells to histamine and dbcAMP. At higher concentrations local anesthetics progressively inhibited both the basal 14C-aminopyrine accumulation and that stimulated by histamine, dbcAMP or carbachol. While a low concentration of local anesthetics increased gastric microsomal (H+-K+)-ATPase activity, higher concentrations inhibited enzyme activity to about 80% of those activities found in resting parietal cells. We conclude that increased aminopyrine accumulation may reflect the activation of membrane-bound enzyme(s) involved in the cAMP-dependent signal transduction pathway mediating acid secretion by parietal cells. In turn, it is possible that the inhibition of aminopyrine accumulation by local anesthetics at higher concentrations can relate to two different mechanisms: (1) the nonspecific effect of local anesthetics that causes simple proton neutralization (as weak bases), and (2) to a minor extent their inhibitory effect on proton pump activity.

ISSN:0031-7012    

DOI:10.1159/000138609

出版商:S. Karger AG    

年代:1989

数据来源: Karger