Journal of cyclic nucleotide research最新文献_第3页

Functional desensitization due to stimulation of cyclic AMP-phosphodiesterase in human mononuclear leukocytes. 人单核白细胞环amp -磷酸二酯酶刺激引起的功能脱敏。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

S C Chan, S R Grewe, S R Stevens, J M Hanifin

{"title":"Functional desensitization due to stimulation of cyclic AMP-phosphodiesterase in human mononuclear leukocytes.","authors":"S C Chan, S R Grewe, S R Stevens, J M Hanifin","doi":"","DOIUrl":"","url":null,"abstract":"We have previously demonstrated heterologous desensitization of human mononuclear leukocytes (MNL) by incubation of low (e.g., 10(-6)M) concentrations of histamine, isoproterenol and prostaglandin E1. Subsequent exposure of the cells to stimulating (e.g., 10(-3) to 10(-5)M) concentrations of any one of the three agonists shows reduced cAMP responses. Possible mechanisms for the subnormal responsiveness include rapid degradation of cAMP. In this report we demonstrated time-dependent elevation of cAMP-phosphodiesterase (PDE) activity following agonist desensitization. The increased enzyme activity was accompanied by a mirror-image decrease in cAMP responsiveness. The effect was rapid and prolonged, with recovery time proportional to desensitization time. Cycloheximide failed to inhibit the increase of cAMP-PDE activity caused by short-term histamine exposure, but partially diminished the elevation as the result of chronic histamine desensitization. We observed three different kinetic forms of cAMP-PDE in MNL, designated as I, II and III, each with distinctive Km and Vmax. Histamine desensitization increased the activity of form II and drastically reduced that of form I. Also we observed a possible conversion of lymphocyte cAMP-PDE from form I to the form II more characteristic of monocytes. Agonist-induced increases in cAMP-PDE activity and changes in enzyme kinetic characteristics represent a potentially important mechanism of functional desensitization. This may have significant effects on biological regulation of cyclic nucleotides.","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"8 4","pages":"211-24"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17361889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calculating the dissociation constant of an unlabeled compound from the concentration required to displace radiolabel binding by 50%. 计算未标记化合物的解离常数所需的浓度取代放射性标记结合的50%。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

J Linden

引用次数: 0

The guanine nucleotide-binding regulatory component of adenylate cyclase in human erythrocytes. 人红细胞中腺苷酸环化酶的鸟嘌呤核苷酸结合调控成分。

Journal of cyclic nucleotide research Pub Date : 1982-01-01 DOI: 10.1016/B978-0-08-028024-0.50009-8

E. Hanski, A. Gilman

引用次数: 11

Direct evidence for the role of the coupling proteins in forskolin activation of adenylate cyclase. 偶联蛋白在forskolin活化腺苷酸环化酶中的作用的直接证据。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

D A Green, R B Clark

{"title":"Direct evidence for the role of the coupling proteins in forskolin activation of adenylate cyclase.","authors":"D A Green, R B Clark","doi":"","DOIUrl":"","url":null,"abstract":"Forskolin stimulation of adenylate cyclase in wild type (WT) S49 lymphoma membrane preparations exhibited a lag and biphasic kinetics as a function of the forskolin concentration (i.e., both a high and low affinity component were observed). In contrast to WT, forskolin stimulation of cyc- adenylate cyclase in membranes demonstrated no observable lag and only the low affinity component. Both the lag and the high affinity component characteristic of forskolin activation of WT were observed in cyc- reconstituted with cholate extracts of WT which contained the G/F protein. The potency of forskolin stimulation of reconstituted adenylate cyclase was increased still further if the reconstitution was carried out with epinephrine and Gpp(NH)p. The Vmax of the forskolin stimulation of adenylate cyclase was approximately the same in the reconstituted and unreconstituted cyc-. In addition to the experiments with reconstituted cyc-, we have demonstrated that forskolin increased the apparent affinity of epinephrine for activation of adenylate cyclase in WT, and reciprocally, epinephrine increased the apparent affinity of forskolin for activation. We conclude that the lag, biphasic kinetics of forskolin activation and the synergism of hormone and forskolin activation of WT are attributable to functional G/F and are consistent with the forskolin stabilization of the activated catalytic unit of adenylate cyclase.","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"8 5","pages":"337-46"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17942050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bibliography of current literature in cyclic nucleotide research. 环核苷酸研究的当前文献参考书目。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

引用次数: 0

Properties of purified soluble guanylate cyclase activated by nitric oxide and sodium nitroprusside. 一氧化氮和硝普钠活化纯化的可溶性鸟苷酸环化酶的性质。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

J A Lewicki, H J Brandwein, C K Mittal, W P Arnold, F Murad

{"title":"Properties of purified soluble guanylate cyclase activated by nitric oxide and sodium nitroprusside.","authors":"J A Lewicki, H J Brandwein, C K Mittal, W P Arnold, F Murad","doi":"","DOIUrl":"","url":null,"abstract":"Highly purified rat lung soluble guanylate cyclase was activated with nitric oxide or sodium nitroprusside and the degree of activation varied with incubation conditions. With Mg2+ as the action cofactor, about 2- to 8-fold activation was observed with nitric oxide or sodium nitroprusside alone. Markedly enhanced activation (20-40 fold) was observed when 1 muM hemin added to the enzyme prior to exposure to the activating agent. The activation with hemin and sodium nitroprusside was prevented in a dose-dependent manner by sodium cyanide. The level activation was also increased by the addition of 1 mM dithiothreitol, but unlike hemin which had no effect on basal enzyme activity, dithiothreitol led to a considerable increase in basal activity. Activated guanylate cyclase decayed to basal activity within one hour at 2 degrees C and the enzyme could be reactivated upon re-exposure to nitroprusside or nitric oxide. Under basal conditions, Michaelis-Menten kinetics were observed, with a Km for GTP of 140 muM with Mg2+ cofactor. Following activation with nitroprusside or nitric oxide, curvilinear Eadie-Hofstee transformations of kinetic data were observed, with Km's of 22 MuM and 100 MuM for Mg-GTP. When optimal activation (15-40 fold) was induced by the addition of hemin and nitroprusside, multiple Km's were also seen with Mg-GTP and the high affinity form was predominant (22 MuM). Similar curvilinear Eadie-Hofstee transformations were observed with Mn2+ as the cation cofactor. These data suggest that multiple GTP catalytic sites are present in activated guanylate cyclase, or alternatively, multiple populations of enzyme exist.","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"8 1","pages":"17-25"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17193509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of cyclic nucleotide phosphodiesterase in the inhibition of cyclic AMP accumulation by carbachol and phosphatidate. 环核苷酸磷酸二酯酶在抑制磷酸根和磷酸根积累环AMP中的作用。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

G M Nemecek, T W Honeyman

{"title":"The role of cyclic nucleotide phosphodiesterase in the inhibition of cyclic AMP accumulation by carbachol and phosphatidate.","authors":"G M Nemecek, T W Honeyman","doi":"","DOIUrl":"","url":null,"abstract":"The possibility that activation of cyclic 3':5'-nucleotide phosphodiesterase is a component of muscarinic inhibition of cyclic AMP accumulation was investigated in WI-38 fibroblasts. At 0.2 to 20 microM, 1-isoamyl-3-isobutylxanthine, an inhibitor of fibroblast phosphodiesterase activity, attenuated the fall in WI-38 cyclic AMP content seen in response to 1 microM carbachol. The inhibitory effect of carbachol on WI-38 cyclic AMP metabolism was also suppressed by the inclusion of 0.1 to 10 microM trifluoperazine in cell incubation media. Exposure of WI-38 cultures to 1 microM carbachol was associated with elevated phosphodiesterase activity in the corresponding broken cell preparations. Both 1-isoamyl-3-isobutylxanthine and trifluoperazine interfered with the ability of 10 microM phosphatidate to mimic carbachol-inhibition of WI-38 cyclic AMP accumulation. Fibroblast calmodulin-dependent phosphodiesterase preparations were activated by micromolar dispersions of phosphatidate. This action of the phospholipid did not appear to require calcium and was blocked by trifluoperazine. These data lend support to the notion that increased cyclic nucleotide phosphodiesterase activity is at least partially responsible for the fall in WI-38 cyclic AMP levels seen in response to cholinergic stimulation. The results also suggest that the effects of cholinergic agents on WI-38 cyclic AMP hydrolysis may be related to changes in phospholipid metabolism, notably the accumulation of phosphatidate.","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"8 6","pages":"395-408"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17258080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

beta-Adrenergic receptors and cyclic AMP responses to epinephrine in cultured human fibroblasts at various population densities. β -肾上腺素能受体和环AMP对不同种群密度培养的人成纤维细胞肾上腺素的反应。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

R P Pochet, D A Green, T J Goka, R B Clark, R Barber, J E Dumont, R W Butcher

{"title":"beta-Adrenergic receptors and cyclic AMP responses to epinephrine in cultured human fibroblasts at various population densities.","authors":"R P Pochet, D A Green, T J Goka, R B Clark, R Barber, J E Dumont, R W Butcher","doi":"","DOIUrl":"","url":null,"abstract":"The beta-adrenergic receptors of the intact human lung diploid fibroblast line Wl-38 and an SV-40 transformed clone of Wl-38, Wl-38-VA-13-2RA (VA13), were estimated in experiments utilizing the beta-adrenergic ligand, 125l-hydroxybenzylpindolol (125IHYP). When specific 125IHYP binding was measured in cells grown to relatively low population densities (0.15x10(6)cells/35mm dish), both Wl-38 and VA13 cells had approximately 40,000 beta-adrenergic receptors per cell. Wl-38 cells, when cultured to a high population density (0.5x10(6) cells/35/mm dish) had clearly diminished numbers of beta-adrenergic receptors and greatly decreased cAMP responses to epinephrine stimulation. On the other hand, in VA13 cells, neither the receptor number nor the beta-adrenergic response was affected by cell population density. In Wl-38 cells, the diminished cAMP response to epinephrine paralleled the decrease in number of beta-adrenergic receptors. Prostaglandin E1 (PGE1) stimulation of cAMP levels was unaffected by cell population density in either Wl-38 or VA13 cells. Thus, increased cell population density, perhaps related to density dependent inhibition of growth, caused a specific diminution in 125IHYP binding concomitant with decreased cAMP responses to epinephrine.","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"8 2","pages":"83-9"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17356853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dopamine and bromocriptine inhibit cyclic AMP accumulation in the anterior pituitary: the effect of cholera toxin. 多巴胺和溴隐亭抑制垂体前叶环AMP积累:霍乱毒素的作用。

Journal of cyclic nucleotide research Pub Date : 1982-01-01

M J Cronin, M O Thorner

引用次数: 0

Insulin mediator--fact or fancy? 胰岛素调节剂——事实还是幻想?

Journal of cyclic nucleotide research Pub Date : 1982-01-01

J Larner

引用次数: 0