摘要:

Partially purified fractions of cytochrome P-450 were prepared from hepatic microsomes recovered from male rats 12 h after administration of either saline or polyriboinosinic: polyribocytidylic acid (poly I:C). Poly I:C reduced the microsomal concentration of cytochrome P-450 by 19% and decreased the maximal binding spectrum (ΔAmax) resulting from addition of the type-II substrate 2,4-dichloro-6-phenylphenoxyethylamine to one fraction (B2) while increasing the affinity of that fraction for this substrate. Poly I:C also reduced the microsomal hydroxylation of benzo(a)pyrene and the N-demethylation of benzphetamine by the other fraction (B1). Since 14C-leucine incorporation into cytochrome P-450 was increased in poly I:C-treated rats, it is suggested that poly I:C depresses hepatic mixed-function oxidase activity by increasing the rate of degradation of specific cytochrome P-450s

ISSN:0031-7012    

DOI:10.1159/000137937

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The regional cerebral distribution of carbon-14 activity was studied using auto-radiography following the intravenous administration of L-3,4-dihydroxyphenyl-(3-14C)-ala-nine (14C-L-dopa) to rats pretreated with carbidopa. 5 min after 14C-L-dopa administration, the regional cerebral distribution of carbon-14 varied with regional cerebral blood flow. From 45 min to 4 h after 14C-L-dopa administration, however, carbon-14 activity accumulated in a regionally selective manner which correlated (p < 0.001) with the total endogenous catechol-amine content of each region (n = 26). A prior unilateral lesion of the substantia nigra pars compacta markedly reduced the accumulation of carbon-14 in the ipsilateral, but not the contralateral, striatum at all times from 45 min to 4 h after 14C-L-dopa administration. Similarly, reserpine pretreatment selectively reduced the accumulation of carbon-14 in only those regions in which a marked accumulation occurred in controls after intravenous injections of 14C-L-dopa. Liquid chromatography with electrochemical detection was utilized to determine the tritium content of L-dopa and its metabolites in the striatum and cerebellum from 1 min to 4 h after the intravenous administration of 3H-L-dopa. 3H-dopamine, and subsequently 3H-dihydroxyphenylacetic acid and 3H-homovanillic acid, appeared only in the striatum. 3H-3-O-methyldopa levels rose simultaneously in the cerebellum and striatum. These results demonstrate a feasible approach for imaging dopamine neurons in man in vivo by positron emission tomography provided that L-dopa can be labeled with a positron-emitting isotope with sufficient specific activity. Furthermore, these results suggest that quantitative interpretation of the images is possible.

ISSN:0031-7012    

DOI:10.1159/000137938

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The effects of cinepazide, 1-[(l-pyrrolidinylcarbonyl)methyl]-4-(3,4,5-trimethox-ycinnamoyl)piperazine hydrogen maleate, were studied in isolated dog cerebral arteries. Cinepazide in concentrations ranging from 10–6 to 10–5M augmented the relaxing responses to ATP, adenosine and cAMP. However, this agent did not affect the relaxations induced by isoproterenol and papaverine and the contractions induced by 5-HT, prostaglandin F2α and ATP. In the basilar artery preloaded with 3H-norepinephrine or 3H-adenosine, electrical transmural stimulation resulted in a marked increase in 3H-efflux. This efflux accompanied an initial transient contraction followed by a relaxation. Cinepazide slightly reduced the 3H-efflux evoked by electrical stimulation. However, the relaxing response was mostly augmented by the treatment with cinepazide. The relaxing responses to ATP, adenosine, cAMP and electrical transmural stimulation were attenuated by theophylline. These results suggest that cinepazide selectively potentiates the relaxing response mediated through purinergic P1 recep

ISSN:0031-7012    

DOI:10.1159/000137939

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Effects of medroxyprogesterone acetate (MPA) on hepatic glucose handling and drug metabolism were investigated in female rats with intact and damaged liver. Hepatic glucose-6-phosphatase activity, glycogen content and fasting blood glucose were assessed as indices of glucose metabolism. Cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were assayed to reflect liver drug metabolism. Liver injury was induced by dimethylnitrosamine and carbon tetrachloride. The results demonstrate that hepatic glucose handling and drug metabolism were changed in a parallel fashion in intact, damaged and induced liver. The MPA-induced changes in glucose metabolism were slight in intact animals, whereas the compound has an increasing effect on glucose and drug metabolism in rats with damaged liver. The findings demonstrate that MPA enhances the normalization of hepatic glucose and drug metabolism in damaged liver.

ISSN:0031-7012    

DOI:10.1159/000137940

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

A sensitive (to 5.0 ng/ml) and specific method for analysis of the antidepressant trazodone is described. The method utilizes gas-liquid chromatography with nitrogen-phosphorus detection. Applicability of the method is demonstrated by (1) a pharmacokinetic study in a normal volunteer who received 50 mg trazodone orally and (2) steady-state plasma level determinations of 2 patients receiving trazodone in the treatment of depression.

ISSN:0031-7012    

DOI:10.1159/000137941

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

To investigate the postnatal development of the carrier-mediated transport process by which certain amino acids are absorbed from the air space of the lung into the bloodstream, a solution of the 14C-labeled nonmetabolized amino acid cycloleucine was administered into the lungs of anesthetized rats of various ages and the rate of absorption of the compound measured. Carrier transport was barely detectable in animals 3–6 days of age; it increased markedly by the age of 12 days, and it reached nearly mature levels by 18 days of age. The rate of development of this carrier process was considerably slower than that previously reported for the organic anion carrier system of the rat lun

ISSN:0031-7012    

DOI:10.1159/000137942

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

In order to assess regional myocardial contractile responses to the beta-adrenergic stimulant prenalterol after recent myocardial infarction, 9 male mongrel dogs underwent left circumflex coronary artery (LCX) occlusion after implantation of miniature subendocardial sonomicrometer crystals in normal, marginally ischemic (border) and central ischemic zones. 90-min LCX occlusion with reperfusion resulted in substantial infarction (mean ± SEM 24 ± 3% of total left ventricular area) and characteristic regional functional alterations. In conscious, unsedated animals 72 h after infarction, intravenous prenalterol (30 μg/kg) significantly decreased end-diastolic and end-systolic segment length and increased percent systolic shortening in normal and border zones, but did not alter ischemic zone function. Heart rate increased significantly with prenalterol. Regional myocardial function before drug administration correlated closely with response to the inotropic agent. These results indicate that the mechanism by which prenalterol improves cardiac function 72 h after myocardial infarction is stimulation of normal and marginally ischemic myocardi

ISSN:0031-7012    

DOI:10.1159/000137943

出版商:S. Karger AG    

年代:1984

数据来源: Karger