摘要:

Enzymatic and nonenzymatic mixed‐function oxidase systems have been shown to generate an oxidant that catalyzes the inactivation of glutamine synthetase and other metabolic enzymes. Recent studies have shown that microsomes isolated from rats chronically fed ethanol generate reactive oxygen intermediates at elevated rates compared with controls. Microsomes from rats fed ethanol were found to be more effective than control microsomes in catalyzing the inactivation of enzymes added to the incubation system. The enzymes studied were alcohol dehydrogenase, lactic dehydrogenase, and pyruvate kinase. The inactivation process by both types of microsomal preparations was sensitive to catalase and glutathione plus glutathione peroxidase, but was not affected by superoxide dismutase or hydroxyl radical scavengers. Iron was required for the inactivation of the added enzymes; microsomes from the rats fed ethanol remained more effective than control microsomes in catalyzing the inactivation of enzymes in the absence or presence of several ferric complexes. The inactivation of enzymes was enhanced by the addition of menadione or paraquat to the microsomes, and rates of inactivation were higher with the microsomes from the ethanol‐fed rats. The enhanced generation of reactive oxygen intermediates and increased inactivation of enzymes by microsomes may contribute toward the hepatotoxic effects associated with ethanol consumption.—Dicker, E.; Cederbaum, A. I. Increased oxygen radical‐dependent inactivation of metabolic enzymes by liver microsomes after chronic ethanol consumption.FASEB J.2: 2901‐2906; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.3169467

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Arginine vasopressin (AVP) is a potent secretagogue for adrenocorticotropin (ACTH) release from normal corticotropes and from ACTH‐secreting pituitary adenoma cells. To explore the mechanism underlying this action, we investigated the effects of AVP on Ca2+‐dependent action potentials and Ca2+currents in cultured human ACTH‐containing pituitary tumor cells (hACTH adenoma cells). Pituitary adenoma fragments removed at surgery from two patients with Cushing's disease were dispersed, and the isolated cells were grown in monolayer culture. Most of the cells showed ACTH immunoreactivity that persisted even after as much as 2 months in culture. Current clamp and voltage clamp recordings were carried out using the patch‐clamp technique in the whole cell configuration. AVP produced an increase in the amplitude and duration of action potentials in these cells, and substantially enhanced the transient after‐hyperpolarization after each spike. Under voltage clamp, hACTH adenoma cells showed two Ca2+current components: a low‐threshold, rapidly inactivating (T‐type) current; and a higher threshold, slowly inactivating (L‐type) current. AVP markedly increased the amplitude of the L‐type current without affecting the T‐type current. These data suggest that AVP may enhance Ca2+entry associated with action potentials by potentiating the activity of L‐type Ca2+channels. The resulting rise in cytosolic free Ca2+may be a key link in the process by which AVP stimulates ACTH release in the pituitary.— Mollard, P.; Vacher, P.; Rogawski, M. A.; Dufy, B. Vasopressin enhances a calcium current in human ACTH‐secreting pituitary adenoma cells.FASEB J.2: 2907‐2912; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.2844618

出版商:Wiley    

年代:1988

数据来源: WILEY