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Chronic ethanol causes heterologous desensitization of receptors by reducing alpha s messenger RNA 总被引:7,自引:0,他引:7
One of the biochemical results of ethanol exposure is a change in the amount of the intracellular second messenger cyclic AMP (cAMP) produced in response to receptor stimulation. In general, acute ethanol exposure increases the amount of cAMP produced on stimulation of receptors coupled to the enzyme adenylyl cyclase via the GTP-binding protein Gs, whereas chronic ethanol exposure has the opposite effect (results for receptors coupled via Gi have been more variable). We previously reported that adaptation to continuous ethanol exposure reduces receptor-stimulated cAMP production by 25-35% in a neuroblastoma cell line (NG108-15), and an even greater reduction of 75% was observed in lymphocytes taken from actively-drinking alcoholics. This reduction in receptor-stimulated cAMP levels was recently confirmed in platelets from alcoholics. None of these studies, however, determined whether more than one receptor coupled to adenylyl cyclase activity was affected in the same cell. Here we report that chronic ethanol exposure causes desensitization of heterologous receptors coupled to Gs as cAMP production mediated by prostaglandin E1 as well as by adenosine is reduced by approximately 30% in NG108-15 cells. We show that, after chronic ethanol exposure, the activity of the alpha subunit of Gs is decreased by 29%, the amount of alpha s protein is decreased by 38.5%, and alpha s messenger RNA is decreased by 30%. Thus, cellular adaptation to ethanol involves a reduction in alpha s mRNA and, as a consequence, reduced cAMP production by heterologous receptors coupled to Gs. Such changes in cAMP production may account for the tolerance and physical dependence on ethanol in alcoholism. 相似文献
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Some Pacific island societies, such as those of Easter Island and Mangareva, inadvertently contributed to their own collapse by causing massive deforestation. Others retained forest cover and survived. How can those fateful differences be explained? Although the answers undoubtedly involve both different cultural responses of peoples and different susceptibilities of environments, how can one determine which environmental factors predispose towards deforestation and which towards replacement of native trees with useful introduced tree species? Here we code European-contact conditions and nine environmental variables for 81 sites on 69 Pacific islands from Yap in the west to Easter in the east, and from Hawaii in the north to New Zealand in the south. We thereby detect statistical decreases in deforestation and/or forest replacement with island rainfall, elevation, area, volcanic ash fallout, Asian dust transport and makatea terrain (uplifted reef), and increases with latitude, age and isolation. Comparative analyses of deforestation therefore lend themselves to much more detailed interpretations than previously possible. These results might be relevant to similar deforestation-associated collapses (for example, Fertile Crescent, Maya and Anasazi) or the lack thereof (Japan and highland New Guinea) elsewhere in the world. 相似文献
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