Chronic ethanol causes heterologous desensitization of receptors by reducing alpha s messenger RNA

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.     

Identification of a new class of steroid hormone receptors

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.     

核能谱与两类转动惯量的精确表达式

用最小二乘拟合法,将稀土区的能谱实验数据,拟合不同的能谱公式,从而证明E=a〔(1+bI(I+1))~(1/2)-1〕是符合得较好的,本文还推导了与上述能谱相应的两类转动惯量,并以此与实验计算值进行比较,结果仍很满意.     

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ

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.     

The influence of prostacyclin (PGI2) on contractile properties of isolated right ventricle of rat heart

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.     

Can purchasing power parity help forecast the dollar?

This paper examines the information on future exchange rate movements provided by the doctrine of purchasing power parity (PPP). Previous research has studied this issue by analyzing the time-series properties of period-by-period levels of, or changes in, exchange rates. In contrast, the present study focuses on the durations of periods in which exchange rates deviate from their PPP levels. If PPP provides information about future exchange rate movements, these durations should exhibit positive duration dependence. That is, the probability of returning to PPP levels should increase as the period of deviation increases. Parametric hazard functions estimated using data from eighteen countries provide no evidence of positive duration dependence. These results are robust to alternative definitions of PPP and to alternative functional specifications. While exchange rates take prolonged swings away from their PPP levels and then eventually return, these movements apparently constitute Monte Carlo cycles in which, at any point in time, the probability of moving back toward PPP is the same as the probability of moving farther away. Thus, PPP provides no useful information on future exchange rate changes, a result consistent with market efficiency.     

灰色理论在化学研究中用作建模与预测新的方法

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。     

cDNA cloning of bovine substance-K receptor through oocyte expression system

The neuropeptide receptors which are present in very small quantities in the cell and are embedded tightly in the plasma membrane have not been well characterized. Mammals contain three distinct tachykinin neuropeptides, substance P, substance K and neuromedin K, and it has been suggested that there are multiple tachykinin receptors. By electrophysiological measurement, we have previously shown that Xenopus oocytes injected with brain and stomach mRNAs faithfully express mammalian substance-P and substance-K receptors, respectively. Here we report the isolation of the cDNA clone for bovine substance-K receptor (SKR) by extending this method to develop a new cloning strategy. We constructed a stomach cDNA library with a cloning vector that allowed in vitro synthesis of mRNAs and then identified a particular cDNA clone by testing for receptor expression following injection of the mRNAs synthesized in vitro into the oocyte system. Because oocytes injected with exogenous mRNAs can express numerous receptors and channels, our new strategy will be applicable in the general molecular cloning of these proteins. The result provides the first indication that the neuropeptide receptor has sequence similarity with rhodopsin-type receptors (the G-protein-coupled receptor family) and thus possesses multiple membrane-spanning domains.     

Suppression of in vitro haematopoiesis following human immunodeficiency virus infection

Viral infections are frequently associated with haematological disorders. Abnormalities including leukopenia, anaemia and thrombocytopenia are commonly observed in patients with the acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The underlying cause of these haematological abnormalities is poorly understood. We report here that bone marrow progenitors isolated from AIDS or ARC patients are responsive to recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) and recombinant erythropoietin. Antibodies present in the serum of patients infected with the human immunodeficiency virus (HIV), however, could suppress the growth of these progenitors, but not the growth of progenitors from HIV seronegative controls. A component of this immune-mediated suppression appears to be antibodies directed towards the envelope glycoprotein (gp120) of HIV.     

Activation of a G protein promotes agonist responses to calcium channel ligands

The activation of a guanine nucleotide binding (G) protein is an essential step in coupling certain receptors to the inhibition of voltage-activated calcium channels. We have previously observed that analogues of GTP potentiate the effect of receptor agonists and inhibit calcium currents in cultured dorsal root ganglion (DRG) neurones. A residual sustained 'L-type' component of the calcium channel current is resistant to inhibition by internal guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S). Because calcium channel antagonists such as D600, nifedipine and diltiazem inhibit L currents, we examined their effect on GTP-gamma-S-modified currents. These compounds all produced a rapid and very marked potentiation of calcium channel currents in the presence of internal GTP-gamma-S and this effect was prevented by pertussis toxin which ADP ribosylates the G proteins Gi/Go (for review see ref. 10). We suggest that this potentiation indicates that activated G protein can interact with the calcium channel, and that this enhances the action of calcium channel ligands at their agonist sites on the channel in its resting state. These results represent the first electrophysiological evidence that guanine nucleotides are able to influence cellular responses to calcium channel ligands.