Journal of cyclic nucleotide research最新文献

{"title":"Distinctions in beta-adrenergic receptor interactions with the magnesium-guanine nucleotide coupling proteins in turkey erythrocyte and S49 lymphoma membranes.","authors":"G Vauquelin,&nbsp;S Y Cech,&nbsp;C André,&nbsp;A D Strosberg,&nbsp;M E Maguire","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Several homogeneous cell systems contain distinct subpopulations of beta-adrenergic receptors, distinguished by their relative sensitivity to N-ethylmaleimide (NEM) in the presence of agonist but not antagonist (G. Vauquelin and M.E. Maguire (1980) Mol. Pharmacol. 18, 363-369). The sensitivity to agonist/NEM inactivation requires receptor interaction with the magnesium-guanine nucleotide coupling proteins (G/F). We have investigated the effects of agonist/NEM treatment on Mg2+ and GTP modulation of receptor affinity in two such systems, turkey erythrocytes and murine S49 lymphoma cells. In each systems, the agonist/NEM-sensitive beta-receptor subpopulation exhibits both Mg2+ and GTP modulation of beta-receptor affinity for agonist. Further, Mg2+ and GTP are not competitive with regard to alteration of receptor affinity; that is, GTP can block the effect of Mg2+, but not vice versa. In contrast, the agonist/NEM-resistant beta-receptor subpopulation shows distinct differences in Mg2+ and GTP effects when the turkey and S49 systems are compared. The agonist/NEM-resistant population in S49 shows no effect of Mg2+ or GTP on beta-receptor affinity for agonist whereas the resistant beta-receptors of turkey erythrocytes still exhibit modulation by both GTP and Mg2+. Moreover, in this receptor population the actions of GTP and Mg2+ are apparently competitive, with increasing Mg2+ concentrations able to overcome the decrease in affinity induced by GTP. Thus, beta-receptor interaction with the metal/nucleotide coupling proteins may differ significantly in the two systems examined. An additional result of these experiments is the demonstration for S49 beta-receptors that free, unchelated GTP or GDP rather than MgGTP or MgGDP modulates receptor affinity for agonist.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"8 3","pages":"149-62"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17361888","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}

{"title":"A GTP-protein activator of phosphodiesterase which forms in response to bleached rhodopsin.","authors":"S Uchida,&nbsp;G L Wheeler,&nbsp;A Yamazaki,&nbsp;M W Bitensky","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A specific protein associated with rod-outer-segment disc membranes binds GTP only in the presence of bleached rhodopsin. Once formed the protein-GTP complex becomes a soluble activator of cGMP phosphodiesterase. It is shown that this activator complex can be completely separated from rhodopsin and retain its ability to activate phosphodiesterase when added to a pool of totally dark (unilluminated) disc membranes. The photoreactive GTP analogue p3-(4-azidoanilido)-5' GTP (AAGTP) is shown to be a more effective substrate than GTP, Gpp(NH)p or 8-azido GTP. [8, 5' 3H] AAGTP was used to specifically covalently label the GTP-binding protein. The protein labeled exhibits a mass of 40,000 daltons when analyzed by SDS-PAGE.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 2","pages":"95-104"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17340388","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}

{"title":"Inhibition of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities of S49 lymphoma cells by agents increasing cyclic AMP.","authors":"J M Honeysett,&nbsp;P A Insel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have examined the regulation of two key enzymes that control polyamine biosynthesis-L-ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) - by agents increasing cAMP in S49 lymphoma cells. Incubation of wild type S49 cells with beta-adrenergic agonists (terbutaline or isoproterenol) inhibited ODC and SAMDC activities rapidly (less than 2 hr). more quickly than these agents arrested the cells in the G1 phase of the cell cycle. The beta-adrenergic antagonist propranolol blocked inhibition of ODC activity produced by isoproterenol, but only if added simultaneously or less than 4 hr after the agonist. Incubation of wild type S49 cells with cholera toxin or PGE1 also inhibited ODC activity. Decreases in ODC activity produced by beta-adrenergic agonists, cholera toxin, PGE1 or dibutyryl cAMP were all enhanced by the phosphodiesterase inhibitor Ro 20-1724. Results of studies of ODC and SAMDC activity in S49 variants having lesions in the pathway of cAMP generation and action were as follows: kin- cells (which lack cAMP-dependent protein kinase activity) showed no inhibition of ODC by any agent; AC- cells (which have absent nucleotide coupling units in their adenylate cyclase system) only demonstrated inhibition in response to dibutyryl cAMP; UNC cells (which have deficient coupling of hormone receptors and adenylate cyclase) only demonstrated inhibition in response to dibutyryl cAMP and cholera toxin, and beta-depleted cells (which have a decreased number of beta-adrenergic receptors) responded as did wild type cells except for absent response to isoproterenol. We conclude that inhibition of ODC and SAMDC activity in S49 cells is an early response to agents that increase cAMP and that this action occurs via the \"classical\" pathways of activation of adenylate cyclase and protein kinase. These results in S49 cells contrast with evidence in other systems in which cAMP has been suggested to enhance polyamine biosynthesis, perhaps through alternative mechanisms.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 5","pages":"321-32"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17347144","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}

{"title":"Similar characteristics of guanine nucleotide regulatory sites involved in adenylate cyclase activation, specific GTPase activity, and cholecystokinin binding in rat pancreatic plasma membranes.","authors":"M Lambert,&nbsp;M Deschodt-Lanckman,&nbsp;J Furnelle,&nbsp;J Christophe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The specificity of guanine nucleotide regulatory site(s) of rat pancreatic plasma membranes involved in adenylate cyclase activation, basal and cholecystokinin (CCK)-stimulated specific GTPase activity, and [125I]-CCK-33 binding was documented. The Km (for GTP) and Ki (for other nucleotides) of basal and CCK-8-dependent GTPase showed similar specificity, decreasing in the order GTP gamma S approximately GTP approximately Gpp[NH]p greater than ITP greater than GDP beta S greater than UTP, suggesting the identity of basal and CCK-stimulated GTPase activities. The same potency order for these nucleotides was obtained when tested as activator (Ka) or inhibitor (Ki for GDP beta S) of adenylate cyclase, in the presence of CCK-8. The IC 50 of these nucleotides on the binding of [125I]-CCK-33 indicated a similar specificity for nucleotide binding sites interacting with CCK receptors (GTP gamma S approximately Gpp[NH]p approximately GTP greater than ITP approximately GDP beta S greater than UTP). In membranes preactivated with 0.3 micron CCK-8 and 30 micron Gpp[NH]p or GTP gamma S, then washed free of hormone and unbound nucleotide, persistent effects of the nonhydrolyzable nucleotides were observed on the three activities tested. The present data indicate that the guanine nucleotide regulatory units involved in adenylate cyclase activation, GTPase activity and CCK binding have similar properties in rat pancreatic plasma membranes.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 6","pages":"385-97"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17192389","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}

{"title":"Catecholamine-induced desensitization in turkey erythrocytes: cAMP mediated impairment of high affinity agonist binding without alteration in receptor number.","authors":"J M Stadel,&nbsp;A De Lean,&nbsp;D Mullikin-Kilpatrick,&nbsp;D D Sawyer,&nbsp;R J Lefkowitz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Desensitization of turkey erythrocyte adenylate cyclase by exposure of these cells to the beta-adrenergic agonist isoproterenol leads to a decrease in subsequent adenylate cyclase stimulation by isoproterenol, F-, or Gpp(NH)p without any apparent loss or down regulation of receptors (B.B. Hoffman et al. J. Cyclic Nucl. Res. 5: 363-366, 1979). We now report that the desensitization is associated with a functional \"uncoupling\" of the beta-adrenergic receptor. This is evidenced by an impaired ability of receptors to form a high affinity, guanine nucleotide sensitive complex with agonist as assessed by computer analysis of radioligand binding data. The changes in adenylate cyclase responsiveness as well as the alterations in receptor affinity for agonists are reproduced by incubation of turkey erythrocytes with the cAMP analog 8-Bromo-adenosine 3':5'- cyclic monophosphate. These findings suggest that one possible mechanism for the development of desensitization in adenylate cyclase systems may be a cAMP mediated alteration of a component(s) of the beta-adrenergic receptor-adenylate cyclase complex which results in impaired receptor-cyclase coupling.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 1","pages":"37-47"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17327903","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}

{"title":"Epinephrine desensitization of adenylate cyclase from cyc- and S49 cultured lymphoma cells.","authors":"D A Green,&nbsp;J Friedman,&nbsp;R B Clark","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The characteristics of the specific beta-adrenergic desensitization of adenylate cyclase from the adenylate cyclase deficient lymphoma cell line (cyc-) and the wild type S49 (WT) are presented in detail in this report. We have previously shown that the cyc- adenylate cyclase desensitized with 1-3 hr pretreatment of the cells with the beta-adrenergic agonist epinephrine. Adenylate cyclase of cyc- was measured after reconstitution with cholate extracts of the coupling proteins (G/F) from WT. We have now demonstrated that: (i) the initial epinephrine-induced desensitization of adenylate cyclase from either cyc- or WT was similar and occurred rapidly, with a half-life of approximately 2 min, although WT desensitized to a greater extent with prolonged hormone treatment (18 hr pretreatment of cyc- or WT with 0.1 mM terbutaline resulted in a 92% desensitization of the WT adenylate cyclase and only a 48% desensitization of cyc-); (ii) the 60 min epinephrine desensitization of cyc- was reversed after addition of propranolol and continued (40-60 min) incubation, while that of WT was only partially reversed; (iii) similar concentrations of epinephrine (0.2-0.4 muM) were required for half-maximal desensitization of both cell lines; and (iv) the Kact for epinephrine stimulation of reconstituted adenylate cyclase from cyc- or WT was increased after a 1 hr desensitization with 10 muM epinephrine. Kact was approximately 5-fold less than the half-maximal concentration required for desensitization. The data support the conclusion that the mechanisms of the rapid, reversible specific beta-adrenergic desensitization of adenylate cyclase in cyc- and WT cells are similar and occur independently of the G/F proteins of the adenylate cyclase complex, whereas the slower, apparently irreversible phase of desensitization occurs only in WT.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 3","pages":"161-72"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18300921","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}

{"title":"Guanine nucleotide binding sites, responsible for adenylate cyclase activation and carbamylcholine binding inhibition, show similar properties in rat heart membranes.","authors":"M Waelbroeck,&nbsp;P Robberecht,&nbsp;P Chatelain,&nbsp;J Christophe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>1/ In rat heart membranes, muscarinic receptors were shown to interact with guanine nucleotide binding sites closely related, if not identical, to those activating adenylate cyclase. The dose-effect curves of GTP, p[NH]ppG, and GTP gamma S for inhibition of carbamylcholine binding (measured by competition with [3H]QNB) and for adenylate cyclase activation (measured in the presence of isoproterenol) were parallel, at both 25 degrees C and 37 degrees C. 2/ Persistent activation of adenylate cyclase was obtained in heart membranes preincubated with p[NH]ppG or GTP gamma S then washed. The affinity for carbamylcholine was reduced after this pretreatment. The SO.5 of p[NH]ppG and GTP gamma S provoking persistent activation of adenylate cyclase and persistent inhibition of carbamylcholine binding were identical. Persistent inhibition of carbamylcholine binding was not additive with the inhibition observed when fresh nucleotide was added after washing. With p[NH]ppG, SO.5 values were unaffected by washing. With GTP gamma S, the SO.5 value for persistent activation of adenylate cyclase (i.e. after washing) and 330 times higher than that implementing activation (i.e. before washing). A similar change was observed when testing the SO.5 of GTP gamma S inhibition of carbamylcholine binding. This might reflect a partial release of GTP gamma S (but not of p[NH]ppG) from \"spare\" nucleotide binding sites during the washing period. 3/ Adenylate cyclase activity after maximal persistent activation was not increased when 0.1 mM guanine nucleotide, with or without 10 muM isoproterenol, was added to the incubation medium. In contrast, carbamylcholine binding was further decreased when fresh guanine nucleotide was added to the binding assay. This suggests that the proportion of \"spare\" nucleotide binding sites capable of activating the adenylate cyclase was higher than that capable to inhibit carbamylcholine binding, or that a second class of nucleotide binding sites (binding p[NH]ppG and GTP gamma S reversibly) was also able to inhibit carbamylcholine binding.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 3","pages":"173-85"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18300922","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}

{"title":"Guanine nucleotide binding sites, responsible for adenylate cyclase activation and carbamylcholine binding inhibition, show similar properties in rat heart membranes.","authors":"M. Waelbroeck, P. Robberecht, P. Chatelain, J. Christophe","doi":"10.1016/B978-0-08-027988-6.50089-6","DOIUrl":"https://doi.org/10.1016/B978-0-08-027988-6.50089-6","url":null,"abstract":"","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"32 1","pages":"173-85"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90160622","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}

{"title":"Influence of parathyroid status of rats on renal tubular handling of adenosine 3'5'-monophosphate: a micropuncture study.","authors":"H Küntziger,&nbsp;H Cailla,&nbsp;C Amiel,&nbsp;M Delaage","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In order to correlate cyclic AMP handling by the nephron to the parathyroid status, clearance and micropuncture experiments were performed in rats with intact parathyroid glands, or immediately after parathyroidectomy, or six days after parathyroidectomy. In intact animals cyclic AMP urinary excretion was about twice the filtered load and the tubular addition of the nucleotide was achieved at the end of the accessible proximal tubule. In acutely parathyroidectomized rats cyclic AMP urinary excretion was not different from the filtered load and no proximal tubular addition was detected at the late accessible proximal tubule. In chronically parathyroidectomized animals urinary excretion of cyclic AMP was not different from the filtered load, nevertheless a proximal tubular addition of the nucleotide was observed, similar in magnitude to that of intact rats. The data afford a direct evidence that the convoluted proximal tubule is the major site of cyclic AMP tubular addition, confirm that this addition disappears immediately after parathyroidectomy, but indicate that it re-occurs in chronic parathyroidectomy.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 5","pages":"313-9"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17347143","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}

{"title":"Large potentiation of agonist response in intact cells is produced by increases only in GTP-dependent adenylate cyclase activity.","authors":"G S Johnson,&nbsp;N Kimura,&nbsp;N Kimura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Treatment of cultured SV40-transformed normal rat kidney cells with the drug, 2-pyridine carboxylic acid, results in a pronounced potentiation in the ability of isoproterenol, prostaglandin E1, and cholera toxin to elevate cyclic AMP levels. With isoproterenol, the initial rate of cyclic AMP accumulation and the maximum cyclic AMP attainable are increased, and also the time of maximum cyclic AMP is prolonged. GTP-dependent adenylate cyclase activities are potentiated in crude membranes from the treated cells, but no evidence for alterations in cyclic nucleotide phosphodiesterase or release of cyclic AMP into the medium could be demonstrated. Results show that augmented adenylate cyclase activity alone, without changes in phosphodiesterase, can lead to dramatic alterations in cyclic AMP accumulation in response to cyclase agonists.</p>","PeriodicalId":15497,"journal":{"name":"Journal of cyclic nucleotide research","volume":"7 2","pages":"105-15"},"PeriodicalIF":0.0,"publicationDate":"1981-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17340386","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}