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981.
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
982.
Identification of a new class of steroid hormone receptors 总被引:54,自引:0,他引:54
The gonads and adrenal glands produce steroids classified into five major groups which include the oestrogens, progestins, androgens, glucocorticoids and mineralocorticoids. Gonadal steroids control the differentiation and growth of the reproductive system, induce and maintain sexual characteristics and modulate reproductive behaviour. Adrenal steroids also influence differentiation as well as being metabolic regulators. The effects of each steroid depend primarily on its specific receptors, the nature of which could therefore provide a basis for classification of steroid hormone action. The successful cloning, sequencing and expression of the human glucocorticoid (hGR) (ref. 1), oestrogen (hER), progesterone (hPR), and mineralocorticoid (hMR) receptors, complementary DNA, plus homologues from various species, provides the first opportunity to study receptor structure and its influence on gene expression. Sequence comparison and mutational analysis show structural features common to all groups of steroid hormone receptors. The receptors share a highly conserved cysteine-rich region which functions as the DNA-binding domain. This common segment allows the genome to be scanned for related gene products: hMR cDNA for example, was isolated using an hGR hybridization probe. In this study, using the DNA-binding domain of the human oestrogen receptor cDNA as a hybridization probe, we have isolated two cDNA clones encoding polypeptides with structural features suggestive of cryptic steroid hormone receptors which could participate in a new hormone response system. 相似文献
983.
Noradrenaline (NA) regulates arterial smooth muscle tone and hence blood vessel diameter and blood flow. NA apparently increases tone by causing a calcium influx through the cell membrane. Two calcium influx pathways have been proposed: voltage-activated calcium channels and NA-activated calcium-permeable channels that are voltage-insensitive. Although voltage-activated calcium channels have been identified in arterial smooth muscle, voltage-insensitive calcium channels activated by NA have not. We show here that NA contractions of rabbit mesenteric arteries increase with depolarization. The increase parallels the elevation of open-state probability (P0) of single, voltage-dependent calcium channels. The action of noradrenaline can be explained by NA-activating voltage-dependent calcium channels, rather than by opening a second type of channel. We show directly that NA increases the open-state probability of single calcium channels. Thus, in the presence of NA, calcium entry through voltage-dependent calcium channels can regulate smooth muscle tone at physiological membrane potentials. These results may have relevance to pathophysiological conditions such as hypertension. 相似文献
984.
J. v. Schönfeld M. Rünzi H. Goebell M. K. Müller 《Cellular and molecular life sciences : CMLS》1995,51(6):556-560
It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment.In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased. 相似文献
985.
We compared the effects of 0.45% normal saline (NS), 5% Intralipid® (IL), and 16.7% glucose (Glu) infusions on total serum triglycerides and cholesterol, serum high-(HDL-c) and low-density lipoprotein cholesterol (LDL-c), and activity of serum lecithin: cholesterol acyltransferase (LCAT), and serum lipoprotein lipase (LPL) in rats implanted with a fibrosarcoma. In tumor-bearing rats given NS, a two-fold increase in total serum cholesterol, a four-fold increase in LDL-c, and a five-fold decrease in the HDL-c/LDL-c ratio were observed compared to tumor-free rats. In tumor-bearing rats administered IL, a two-fold increase in total serum triglyceride and cholesterol, a three-fold increase in HDL-c and HDL-c/LDL-c ratio, and a two-fold increase in LPL activity were observed compared to tumor-bearing rats administered NS. In tumor-bearing rats administered Glu, a two-fold decrease in total serum cholesterol, a two-fold decrease in HDL-c, and a three-fold decrease in LDL-c were observed compared to tumor-bearing rats administered NS. Tumor weights and LCAT activity did not differ significantly between treatment groups. Previous results have demonstrated that lipophilic compounds that interact with plasma lipoproteins have altered pharmacological effects when administered with IL. Therefore, this study suggests that IL infusions alter the HDL-c/LDL-c ratio and could affect the pharmacological behavior of anticancer compounds that predominantly distribute into the LDL fraction upon entrance into the bloodstream. 相似文献
986.
C. D. Reymond P. Schaap M. Véron J. G. Williams 《Cellular and molecular life sciences : CMLS》1995,51(12):1166-1174
cAMP plays an essential role duringDictyostelium development both outside and inside the cell. Membrane-bound receptors and adenylyl cyclase are responsible for sensing and producing extracellular cAMP, whereas a phosphodiesterase is responsible for maintaining a low basal level. The molecular events underlying this type of hormone like signalling, which are now beginning to be deciphered, will be presented, in the light of cAMP analogue studies. The importance of intracellular cAMP for cell differentiation has been demonstrated by the central role of the cAMP dependent protein kinase. Mutants as well as strains obtained by reverse genetics will be reviewed which lead to our current understanding of the role of intracellular cAMP in the differentiation of both stalk and spore cells. 相似文献
987.
The role of ethylene, pure or in formulation, in the colonization behaviour of the olive bark beetle,Phloeotribus scarabaeoides (Coleoptera, Scolytidae) has been investigated in the laboratory. Ethylene has been found to be attractive in both sexes; the formulation ethrel 48 was active in an olfactometer up to several months. Ethylene, whose concentration varies with the developmental stage or the condition of the tree or its wood, may play an important role in the primary attraction of these scolytids to their host. 相似文献
988.
M. Pavlović D. Petković M. Cvetković D. J. Macut K. Zdjelar M. Nešić O. Bosnić R. Radulović M. Mihajlović 《Cellular and molecular life sciences : CMLS》1995,51(9-10):941-944
The mechanism of the positive inotropic effect of prostacyclin (PGI2) (2.6×10?6 mol/l) on the isolated right ventricle of rat heart was studied. Our results show that the positive inotropic effect of prostacyclin is produced indirectly through beta adrenoceptors and slow Ca2+ channels, because blockade of slow Ca2+ channels with verapamil (10?6 mol/l) and beta adrenoceptors with propranolol (10?6 mol/l) abolishes this effect. Alpha adrenoceptors do not mediate the action of PGI2. 相似文献
989.
灰色理论在化学研究中用作建模与预测新的方法 总被引:1,自引:0,他引:1
研究了灰色理论作为一种有用的化学计量学多元建模与定量预测新方法的可行性,将其应用于某些不确定关系如电泳迁移率,色谱保留值和农药需求量等建模,定量预测结果良好。 相似文献
990.
本文使用SEM、EDS、EAS、XRD和电阻率测量技术,研究了工艺参数和加入(Co,Fe2O3)对PTC(V1-x,Crx)2O3陶瓷的显微结构和电性能的影响。实验结果表明,为了制造优良性能、高可靠的热敏电阻器,必须精确控制陶瓷组份和工艺。引人象C。这样的添加物是重要的,它主要以金属形式分布在基体中,同时发现添加物对试样致密度和电性能的影响也是有益的。 相似文献