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1.
Metabolic pathways involved in the oxidation of isopropanol into acetone by the intact rat 总被引:3,自引:0,他引:3
Isopropanol administered in a large (6 g/kg, orally) as well as in a lower dose (1 g/kg, I.P.) is slowly oxidized into acetone by the intact rat. Using two inhibitors, 3 amino-1,2,4-triazole and pyrazole, investigations on the hepatic enzymatic system involved in the oxidation of isopropanol show that catalase does not play an important part in this pathway, contrary to alcohol dehydrogenase which is the major enzyme responsible for this oxidation. Although isopropanol oxidation is mainly catalysed in the liver through alcohol dehydrogenase, no alteration of the hepatic extramitochondrial redox state occurs after the administration of a large as well as of a lower dose of isopropanol. From these experiments it may be concluded that alterations of the liver NAD+/NADH ratio, which seem to play an important part in the ethanol induced fatty liver, are not involved in the isopropanol induced one. 相似文献
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The characteristics of the binding of the hydrophilic beta-adrenergic antagonist [3H]CGP 12177 to intact rat adipocytes were studied at 37 degrees C and 6 degrees C. At both temperatures and at 90% saturation, the non-specific binding was less than 30% of the total binding. At 37 degrees C, specific [3H]CGP 12177 binding was rapid, reversible of high affinity (1.8 +/- 0.4 nM) and saturable. The number of specific binding sites per adipocyte increased with the fat cell size (about 35 000 and 115 000 sites per cell in adipocytes with diameters of 60 microns and 88 microns, respectively) but remained constant when expressed per unit fat cell surface area. Displacement of [3H]CGP 12177 bound to adipocytes by unselective and selective beta-antagonists was stereospecific, had the same characteristics as those found in adipocyte membranes and showed a heterogeneous specificity for beta 1 and beta 2 adrenergic subtypes. In contrast, beta agonist competition curves, which modeled to two affinity-states of binding, showed high-affinity-state Kd values for agonists 10-25-times higher than those found in membranes under the same experimental conditions. At 6 degrees C, although the number and affinity of the specific binding sites for [3H]CGP 12177 were the same as those found at 37 degrees C, the Kd value for (-)-isoproterenol binding to the high affinity state of these sites (3.0 +/- 0.5 nM) was 25-times lower than at 37 degrees C and similar to the value found in membrane preparations (1.5-4 nM). These results show that the [3H]CGP 12177 specific binding sites detected on intact adipocytes represent the physiological beta-adrenergic receptors. Moreover, this study extends to the adipocyte the validity of the model recently proposed for other cell lines, according to which in intact cells, but not in membranes, agonist-binding promotes a rapid and temperature-dependent conformational change of the beta-adrenergic receptors, leading to a progressive loss of capacity of agonists to form a high-affinity complex. 相似文献
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Cardiovascular and biological effects of K+ channel openers, a class of drugs with vasorelaxant and cardioprotective properties 总被引:3,自引:0,他引:3
Several new chemical entities (RP 52891, cromakalim and its derivatives) are potent and specific openers of vascular K+ channels. This mechanism is also shared, at least partially, by drugs such as minoxidil, diazoxide, pinacidil and nicorandil. The opening of plasmalemma K+ channels produces loss of cytosolic K+. This effect results in cellular hyperpolarization and functional vasorelaxation. In normotensive or hypertensive rats, K+ channel activators decrease aortic blood pressure (by producing a directly mediated fall in systemic vascular resistance) and reflexly increase heart rate. The former effect is not modified by specific blockers of classical vascular receptors but it is completely antagonized by the hypoglycemic sulphonylurea, glibenclamide, an established blocker of ATP-regulated K+ channels. K+ channel openers produce selective coronary vasodilatation and afford functional and biochemical protection to the ischemic myocardium. This salutary effect is mediated via cardiac K+ channel modulation and may result from an improved myocardial oxygen balance in the ischemic region. K+ channel openers increase plasma renin activity in animals as well as in man. However, only diazoxide, but not cromakalim or RP 52891, lowers plasma insulin concentration. The dose of glibenclamide entirely blocking the latter effect is over 50-fold smaller than that antagonizing the hypotensive and hyper-reninemic responses to diazoxide. In conclusion, K+ channel activators are potent vasorelaxant and cardioprotective agents possessing an original mechanism of action which is the opening of plasmalemma ATP-regulated K+ channels. Their clinical use as antihypertensive agents may be accompanied by undesirable effects (characteristic of peripheral vasodilators) which are likely to be attenuated or avoided by controlled release formulations. However, inasmuch as low doses of K+ channel openers may be sufficient to produce selective coronary artery dilatation and cardioprotection, these compounds could be of particular value in treating patients with coronary artery disease efficaciously and possibly without adverse cardiovascular effects. 相似文献
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After having established the alpha 2-adrenoceptor nature of the binding sites specifically labeled by the alpha 2-agonist [3H] UK 14304 in hamster adipocytes, two different approaches have been used to determine whether these alpha 2-adrenoceptors were "spare receptors". The first one, consisted to block irreversibly fractions of the receptor population by various concentrations of the alpha 2-antagonist benextramine and determine the relationship between the residual receptor occupancy by UK 14304 and the corresponding magnitude of the cellular inhibitory cyclic AMP response to the alpha 2-adrenergic component of epinephrine under conditions avoiding cyclic AMP breakdown. The second approach was a detailed comparison between alpha 2-receptor occupancy by [3H] UK 14304 and the cyclic AMP inhibitory dose-response curve to this agonist in cells incubated also under conditions avoiding cyclic AMP breakdown. These two experimental approaches clearly showed that the alpha 2-adrenoceptor of hamster adipocytes are not "spare receptors". 相似文献
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Christiane Guguen-Guillouzo Marie-France Szanjnert Denise Glaiser Claudine Gregori Fanny Schapira 《In vitro cellular & developmental biology. Plant》1981,17(5):369-377
Summary Aldolase and pyruvate kinase isozymes were investigated in cultured hepatocytes from fetal, regenerating, and 2-acetyl-aminofluorene-fed
rat liver as well as in some epithelial liver cell lines. Our results show that: (a) cell proliferation and prolonged expression
of specific isozymes were found only in cultured hepatocytes from 17-day old fetuses; (b) the fetal type of pyruvate kinase
expressed in regenerating and carcinogen-treated liver was temporarily lost only in cultured hepatocytes from regenerating
liver; (c) the adult type of aldolase and pyruvate kinase was absent in one epithelial cell line derived from a carcinogen-treated
liver and in the hepatoma tissue cell (HTC) line but was found in the Faza clone of the Reuber H35 cell line during the 50 first passages in vitro; and (d) the isozyme pattern of pyruvate kinase was always more strongly
shifted than that of aldolase.
The observations suggest that: (a) hepatocytes from carcinogen-treated liver exhibit the same lack of ability to proliferate
in primary culture as normal adult hepatocytes; (b) adult hepatocytes can produce fetal isozymes without prior cell division;
(c) pyruvate kinase is a stronger marker of dedifferentiation (retrodifferentiation) than aldolase; and (d) regulatory processes
of isozyme expression are different during ontogenesis, regeneration, and hepatocarcinogenesis.
This work was supported by the “Institut National de la Santé et de la Recherche Médicale” and the “Fondation pour la Recherche
Medicale Fran?aise” 相似文献
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Martha N. Calderón Fanny Guzmán Orlando Acosta Carlos A. Guerrero 《International journal of peptide research and therapeutics》2012,18(4):373-382
Rotavirus infection of MA104 cells has been shown to be inhibited by cell membrane-impermeant thiol/disulfide exchange inhibitors and anti-PDI antibodies. To characterise the amino acid sequences of rotavirus structural proteins potentially mediating cell surface PDI?Csubstrate interactions, rotavirus-derived peptides from VP4 and VP7 (RRV) and VP7 (Wa), and their modified versions containing serine instead of cysteine were synthesized. Cysteine-containing VP7 peptides corresponding to residues 189?C210 or 243?C263 caused an infectivity inhibitory effect of about 64 and 85?%, respectively, when added to cells. Changing cysteine to serine significantly decreased the inhibitory effect. A cysteine-containing peptide corresponding to VP4 residues 200?C219 and its scrambled version reduced infectivity by 92 and 80?%, respectively. A cysteine to serine change in the original VP4 200?C219 peptide did not affect its inhibitory effect. Non-rotavirus related sequences containing cysteine residues efficiently inhibited rotavirus infectivity. Antibodies against VP7 residues 189?C210 or 243?C263 significantly inhibited rotavirus infectivity only after virus attachment to cells had occurred, whereas those against VP4 200?C219 peptide inhibited infectivity irrespective of whether virus or cell-attached virus was antibody-treated. A direct PDI?Cpeptide interaction was shown by ELISA for cysteine-containing VP7 and VP4 peptides. Virus?Ccell attachment was unaffected by the peptides inhibiting virus infectivity. The results showed that even though cysteine residues in the peptides tested are important in both virus infectivity inhibition and in vitro PDI?Cpeptide interaction, the accompanying amino acid sequence also plays some role. As a whole, our findings further support our hypothesis that cell surface PDI from MA104 cells might be contributing to rotavirus entry at a post-attachment step. 相似文献
10.
Ethanol alters the adenosine receptor-Ni-mediated adenylate cyclase inhibitory response in rat brain cortex in vitro 总被引:2,自引:0,他引:2
It has been suggested that ethanol stimulates adenylate cyclase in vitro through an increased function of Ns, the activatory component of adenylate cyclase. Because of the interaction of Ns with Ni, the adenylate cyclase inhibitory component, we have studied the effect of ethanol (0.05-0.2 M) on Ni-mediated adenylate cyclase inhibition caused by the adenosine analog N6-phenylisopropyladenosine (N6-PIA) in brain cortical membranes. Ethanol did not alter N6-PIA binding to the adenosine Ri-receptors, stimulated slightly basal adenylate cyclase activity but abolished adenylate cyclase inhibition due to N6-PIA, suggesting an effect of ethanol on the inhibitory coupling pathway. This was further supported by loss of the adenylate cyclase inhibitory response to GTP (greater than 10(-5) M). It thus seems that, besides its effect on the Ns system, ethanol may also impair Ni-mediated adenylate cyclase responses in rat cerebral cortex. 相似文献