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1.
Summary In normal lymphocytes somatostatin non-competitively inhibited basal (ID50 5×10–4 M) and isoproterenol- and forskolin-stimulated adenylate cyclase activity (Ac). In acute leukemia blasts, non-responsive to isoproterenol, forskolin, which activates the catalytic subunit, stimulated and somatostatin inhibited Ac, thus indicating the leukemic enzyme, though defective, retains the inhibitory pathway and catalyst function.  相似文献   

2.
Summary The -adrenergic agonist isoproterenol and prostaglandins E1 and E2 (but not F2) increased the cAMP content of rat submandibular acini in vitro, but only isoproterenol enhanced ouabain-sensitive86Rb (K) uptake. These findings suggest that cAMP is not involved in the activation of the Na, K pump in salivary cells.  相似文献   

3.
Summary Forskolin, an adenylate cyclase activator when injected s.c. (1 mg/kg) in mice, caused an elevation of cAMP in the forebrain and cerebellum of up to 170% and 130%, respectively. The treatment was found to prevent seizures induced by pentylenetetrazol. This suppression had subsided 30 min after the injection, when cAMP level was again normal in the cerebellum but still elevated in the forebrain.  相似文献   

4.
Summary Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E1 significant reliability was observed only for male subjects.Acknowledgment. This work was supported in part by the following organizations: Chief Scientist's Office, Israel Ministry of Health; Herman Goldman Foundation, New York; United Jewish Endowment Fund of Greater Washington-Pollinger Foundation.  相似文献   

5.
前列腺素E2受体(EP)是一类G蛋白偶联受体,主要与前列腺素E2(PGE2)结合,在多种疾病的发生中发挥作用.研究发现EP在机体几乎所有系统,如心血管系统、呼吸系统、生殖系统、神经系统等的病理反应中发挥重要作用,甚至与肿瘤的发生也有关联.研究并掌握EP相关性质对于临床疾病的治疗有着重要的意义,在国际上已成为研究和报道的热点.本文简要综述了关于EP前沿的研究成果,以期为广大研究者提供借鉴,为进一步阐释EP作用机制以及相关研究乃至临床治疗提供新的思路.  相似文献   

6.
In the present study we show, for the first time, that phenylephrine (PHE), an -adrenergic receptor agonist, potentiates the effect of isoproterenol (ISO), a -adrenergic agonist, in activating pineal type II5-deiodinase (5-D) activity. The potentiating effect of PHE was observed only at doses of ISO which induce submaximal activation of the enzyme. However, at doses which lead to maximal activation of the enzyme, PHE was ineffective. The results suggest that not only -, but also -adrenergic receptors, are involved in the sympathetic noradrenergic regulation of pineal 5-D activity in the adult rat.  相似文献   

7.
Summary cAMP concentration was found to be significantly lower during desynchronized sleep than during synchronized sleep in the preoptic area of rats kept at normal laboratory temperature. No significant changes in cerebral cortex cAMP concentraion were observed in the same experimental conditions.This work was supported by grants from Consiglio Nazionale delle Ricerche and Ministero della Pubblica Istruzione.The authors wish to thank G. Mancinelli and L. Sabattini for technical assistance and M. Luppi for secretarial assistance.  相似文献   

8.
The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae ofDrosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm,Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5×10–6 to 5×10–4 M.  相似文献   

9.
Possible drug interactions with electrical defibrillation were examined. We tested the hypothesis that adrenergic agents (epinephrine, norepinephrine, isoproterenol) and a calcium channel blocker (verapamil), when applied acutely, alter the duration of arrest following a defibrillator shock. A secondary hypothesis (based on observations) was that the drugs alter the occurrence of changes to normal rhythms following the shock. Dissociated heart cells from 10-day chicken embryos were cultured to form spherical aggregates and plated in petri dishes. In the experiments, the spheres were paced at 0.75 V/cm above contraction threshold, and a biphasic defibrillator shock was applied for 1 ms at 46 V/cm. The arrest time and occurrence of rhythm changes were recorded. The adrenergic agents shortened the duration of arrest following a defibrillator shock, while the calcium channel blocker lengthened the arrest time. Comparisons with the control proportion of double beats showed no significant change with the adrenergic agents and a decrease with verapamil.Received 19 August 2004; received after revision 8 October 2004; accepted 18 October 2004  相似文献   

10.
Summary Beta-adrenergic-associated cyclic AMP accumulation was studied in intact lymphocytes before and after transformation with Epstein-Barr virus into immortal cell lines. Although a marked reduction in isoproterenol-stimulated cyclic AMP synthesis was observed in transformed cells, forskolin-stimulated cyclic AMP accumulation was preserved. A parallel loss of125-iodocyanopindolol binding sites suggests that the reduction in beta-adrenergic-stimulated AMP synthesis is due to receptor down regulation.  相似文献   

11.
12.
Class III adenylyl cyclases are the most abundant type of cyclic AMP-producing enzymes. The adjustment of the cellular levels of this second messenger is achieved by a variety of regulatory mechanisms which couple signals to adenylyl cyclase activity. Because of the divergent nature of stimuli which impinge on these enzymes, highly individualized class III adenylyl cyclases have evolved in metazoans, eukaryotic unicells and bacteria. Regulation usually exploits the dimeric structure of the catalyst, whose active centres form at the dimer interface. The fold of the catalytic domains and the basic catalytic mechanisms are similar in all class III adenylyl cyclases, and substrate binding generally closes the active site by an induced-fit mechanism. Regulatory inputs can result in dramatic rearrangements of the catalytic domains within the dimer, which often are based on rotational movements. Received 13 February 2006; received after revision 16 March 2006; accepted 20 April 2006  相似文献   

13.
Summary Single muscle fibers from the barnacleBalanus nubilus have been used as a preparation to see if a synthetic 20-residue PKI (5-24)-peptide is able to block or reverse the stimulatory response of the ouabain-insensitive Na efflux to injected cAMP. The results obtained show that this peptide behaves as a powerful inhibitor of the cAMP-mediated response and is also able to partially reverse the sustained stimulation of the Na efflux observed in ouabain-poisoned fibers following the injection of subunit A of cholera toxin.Warmest thanks to Prof. E. H. Fischer and Kurt Diltz for a sample of sPK1. This work received support from NSF, the Graduate School Research Committee and from NIH through a General Research Support Grant to the University of Wisconsin Medical School.  相似文献   

14.
Summary Porcine or human follicular fluid inhibited the spontaneous maturation of isolated hamster oocytes in vitro during the first 1.5 h of culture. Moreover, the presence of 50% follicular fluid combined with 100 M dbcAMP cooperatively reduced the incidence of germinal vesicle breakdown. The addition of FSH also inhibited the resumption of meiosis, and the presence of LH did not overcome the inhibitory effects of follicular fluid and tended to impede isolated hamster oocyte maturation in vitro.  相似文献   

15.
Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005  相似文献   

16.
Summary Cyclic adenosine 3,5-monophosphate (cyclic AMP)-binding proteins which have the characteristics of cyclic AMP-dependent protein kinase (E.C. 2.7.1.37) regulatory subunits, have been identified in rat and human saliva. Concentration of these proteins was increased in rat saliva after stimulation with isoproterenol, suggesting that they were released during exocytosis. Cyclic AMP-dependent protein kinase catalytic activity was not measurable in saliva of either species.  相似文献   

17.
Summary The binding of 16-phenoxy derivatives of prostaglandin (PG) F2 to rat luteal membranes, and also their abortifacient potency in pregnant rats, have been studied. Competitive binding studies with various PG-analogues were performed in ovaries of juvenile rats pretreated with PMSG and HCG, and in parallel studies the abortifacient potency of these substances was tested, in pregnant rats. It was observed that this class of derivatives bound to the PGF2 receptor as well as, or even better than the parent compound PGF2. Modifications in the carboxyl group at C-1 yielded derivatives with a higher affinity for the receptor, in decreasing order of effectiveness as follows:-COOR>COOH>OH. The data obtained from the binding studies also compared well with data on the abortifacient potency in pregnant rats. It is concluded that the addition of a phenoxy group to either the lower or upper side chain of PGF2 may augment the binding to the receptor as well as the biological responses induced by the post receptor effect.  相似文献   

18.
Changes in cytosolic Ca2+ play an important role in a wide array of cell types and the control of its concentration depends upon the interplay of many cellular constituents. Resting cells maintain cytosolic calcium ([Ca2+]i) at a low level in the face of steep gradients of extracellular and sequestered Ca2+. Many different signals can provoke the opening of calcium channels in the plasma membrane or in intracellular compartments and cause rapid influx of Ca2+ into the cytosol and elevation of [Ca2+]i. After such stimulation Ca2+ ATPases located in the plasma membrane and in the membranes of intracellular stores rapidly return [Ca2+]i to its basal level. Such responses to elevation of [Ca2+]i are a part of an important signal transduction mechanism that uses calcium (often via the binding protein calmodulin) to mediate a variety of cellular actions responsive to outside influences.  相似文献   

19.
Adenosine is an endogenous signaling molecule upregulated during inflammatory conditions. Acting through the A2b receptor (A2bR), the predominant adenosine receptor in human colonic epithelia, adenosine has been directly implicated in immune and inflammatory responses in the intestine. Little is known about expression and regulation of A2bR during inflammation. Tumor necrosis factor alpha (TNF-α) is highly upregulated during chronic and acute inflammatory diseases. This study examined the expression of A2bR during colitis and studied effects of TNF-α on A2bR expression, signaling and function. Results demonstrated that A2bR expression increases during active colitis. TNF-α pretreatment of intestinal epithelial cells increased A2bR messenger RNA and protein expression. TNF-α significantly increased adenosine-induced membrane recruitment of A2bR and cyclic adenosine monophosphate downstream signaling. Further, TNF-α potentiated adenosine-induced shortcircuit current and fibronectin secretion. In conclusion, we demonstrated that TNF-α is an important regulator of A2bR, and during inflammation, upregulation of TNF-α may potentiate adenosine-mediated responses. Received 21 July 2005; received after revision 22 August 2005; accepted 19 September 2005 †These authors contributed equally to this work.  相似文献   

20.
Summary In mixed culture of Chinese hamster fibroblatst, clone 431, and transformed murine L fibroblasts, clone B-82, isoproterenol was found to protect only 431 cells against ionizing radiation. It was shown that 431 cells, in contrast to B-82 cells, possess-adrenoreceptors, and the radioprotective effect of isoproterenol can be realized only if this agent interacts with-adrenoreceptors coupled with the cAMP system. Since malignization often causes the disappearance of-adrenergic and other hormone receptors, the combined culturing and irradiation of the cells studied can be regarded as a model of the growth of malignant cells (B-82) among normal tissue cells (431 cells) under conditions of radiation therapy. A possibility of selective protection against radiation damage of normal tissue cells, with retention of the former radiosensitivity of tumor cells, is discussed.  相似文献   

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