摘要:

Four monoclonal antibodies (MAbs) to phenobarbital-induced cytochrome P-450 (PB-P-450) show different patterns of inhibition of PB-P-450 catalyzed aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin deethylase, benzphetamine demethylase and ethylmorphine demethylase. The inhibition constants vary depending on the individual monoclonal antibody and the individual substrate. Two of the four monoclonal antibodies completely inhibit the reduction of cytochrome P-450 by NADPH cytochrome c (P-450) reductase. The same cytochrome P-450 bound to carbon monoxide, however, can be reduced chemically by sodium dithionite in the presence of the monoclonal antibody. These data indicate that the two MAbs examined completely prevent electron transfer by NADPH cytochrome c (P-450) reductase. Substrate binding is partially inhibited by the monoclonal antibody. The type I substrate-binding spectrum of benzphetamine is inhibited more than the type II binding spectrum of aniline. The degree of inhibition of the substrate binding as indicated by the spectrum is less than that observed for the inhibition of catalytic enzyme activity by the monoclonal antibodies. The data indicate that each of the MAbs are directed toward epitopes on the cytochromes P-450 with different relationships to the active catalytic site.

ISSN:0031-7012    

DOI:10.1159/000138677

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The influence of cigarette smoke on nicorandil plasma levels at a dose of 10 mg/kg administered orally was investigated in rats. The animals were exposed to standard and nicotineless cigarette smoke for 8 min using a ‘smoking machine’. In nonsmoking control rats, nicorandil plasma levels increased rapidly and reached the maximum (approx. 7.6 μg/ml) after 1 h and then decreased gradually. On the other hand, nicorandil plasma levels in the rats inhaling standard cigarette and nicotine-less cigarette smoke reached the maximum (approx. 4.7 and 4.9 μg/ml, respectively) after 1–2 h. These results suggest that nicorandil plasma levels after oral administration are influenced not only by standard cigarette smoke but also by nicotine-less cigarett

ISSN:0031-7012    

DOI:10.1159/000138679

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effects of sulphasalazine and of its major constituents, sulphapyridine and 5-aminosalicylic acid (5-ASA), on gastric ulceration as well as on changes in mast cell counts and mucus levels in the glandular mucosa were examined in restrained rats exposed to 4°C (stress) for 2 h. Sulphasalazine (50, 100, 200 mg/kg), sulphapyridine (31.25, 62.5, 125 mg/kg) or 5-ASA (18.75, 37.5, 75 mg/kg) was injected subcutaneously 0.5 h before stress induction. Cold-restraint stress produced gastric glandular mucosal ulcers which were significantly reduced by all three doses of sulphasalazine and the higher doses of sulphapyridine and 5-ASA. Sulphasalazine prevented mast cell degranulation and increased the amount of mucus adhering to the mucosa. In contrast, the higher doses of sulphapyridine significantly increased only the mucus levels, whereas those of 5-ASA effectively prevented mast cell degranulation. The results show that the total effect of sulphasalazine is approximately equivalent to the summation of the actions of its component doses of sulphapyridine and 5-ASA. It is notable that sulphapyridine itself appears to be biologically active in reducing ulcer severity

ISSN:0031-7012    

DOI:10.1159/000138680

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

β-Adrenergic receptors on isolated human lymphocytes were enumerated using l25I-cyanopindolol (125I-CYP), after a 90-min exposure to 50 μmol/l I-isoproterenol in vitro. No change in receptor density could be shown in assays performed at 37°C, although a 40% reduction was apparent in binding studies carried out at 4°C. In contrast, β-adrenergic receptors on lymphocytes from mild asthmatics after a 3-week course of oral terbutaline showed a 40% reduction in receptor density regardless of the assay temperature, in addition to a 2.5-fold reduction in the receptor affinity for isoproterenol. The data are consistent with reports that a fraction of receptors are sequestered during short-term exposure to agonists. Sequestered receptors may or may not be detected by radioligand binding assays depending on the ligand of choice, temperature of the binding assay and duration of prior exposure to the agonist. After extended exposure to an agonist in vivo, the number of surface receptors was reduced, and sequestered receptors were not present, presumably as a result of degrada

ISSN:0031-7012    

DOI:10.1159/000138681

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Ca2+ agonists, Bay K 8644 and CGP 28392, induced concentration-dependent contractions in segments of rat aorta partially depolarized with 15 mmol/l K+. The responses caused by Bay K 8644 were greater than those elicited by CGP 28392. The actions of these Ca2+ agonists were blocked by nifedipine. CGP 28392 and mainly Bay K 8644 increased the contractions induced by different K+ concentrations but did not alter those caused by nor-adrenaline (NA) and higher K+ concentrations. Bay K 8644 enhanced and nifedipine reduced the contractions elicited by Ca2+ addition in a Ca2+-free solution containing K+ (25, 50 or 75 mmol/l). This enhancement was blocked by nifedipine. Nifedipine and verapamil reduced more effectively the responses induced by K+ than those caused by NA; they did not modify contractions evoked by Ca2+ ionophore A23187. They also reduced the increases in K+ contractions elicited by CGP 28392 and Bay K 8644. Bay K 8644 increased 45Ca2+ uptake induced by K+ and did not affect that caused by NA. Nifedipine blocked this increase as well as 45Ca2+ uptake elicited by NA and K+. Basal 45Ca2+ efflux was not modified by verapamil and Bay K 8644. NA and K+ significantly increased this efflux in normal solution, but not in Ca2+-free medium. Bay K 8644 enhanced 45Ca2+ efflux induced by K+ in normal medium, whereas it did not affect those elicited by NA and K+ in a solution without Ca2+. This Ca2+ agonist had scant ability to induce Ca2+ efflux in a Ca2+-free medium. These results indicate that in this vascular preparation: (1) Ca2+ agonists (Bay K 8644 particularly) have the ability to produce Ca2+ influx (and subsequent contraction) and Ca2+ efflux by activation of voltage-operated Ca2+ channels (VOCs), only when they are preactivated with K+; (2) VOCs and receptor-operated Ca2+ channels (ROCs) appear to constitute two different populations, and (3) Ca2+ antagonists possess, in comparison with Ca2+ agonists, a small range of selectivity to block only VOCs; the latter drugs are better to pharmacologically discriminate between VOCs and ROCs in the rat aorta.

ISSN:0031-7012    

DOI:10.1159/000138682

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Male CBA/Ca inbred mice were treated with a dose of 8 μg 2-mercapto-ethanol per animal per day in the drinking water from the age of 5 months onwards up to the age of 24 months. Dopamine release was greatly decreased in old animals in contrast to the elevation of dopamine release in the treated mice. Similarly, an elevated malondialdehyde content in brain homogenates was also observed in the aged treated animals compared with their controls. No essential differences were observed in locomotor activity and learning between treated an control mice

ISSN:0031-7012    

DOI:10.1159/000138683

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138684

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138685

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138676

出版商:S. Karger AG    

年代:1990

数据来源: Karger