European Journal of Pharmacology: Molecular Pharmacology最新文献

{"title":"Feedforward control of agonist-induced Ca2+ signalling by protein kinase C in airway smooth muscle cells","authors":"Ben H. Hoiting,&nbsp;René Kuipers,&nbsp;Carolina R.S. Elzinga,&nbsp;Johan Zaagsma,&nbsp;Herman Meurs","doi":"10.1016/0922-4106(95)90033-0","DOIUrl":"10.1016/0922-4106(95)90033-0","url":null,"abstract":"<div><p>In isolated bovine tracheal smooth muscle cells, the potent and specific protein kinase C inhibitor GF 109203X caused an inhibition of methacholine-and histamine-induced Ca²⁺ mobilization and influx, indicating for the first time that protein kinase C activation induced by contractile agonists exerts a positive feedforward control of Ca²⁺ signalling by these agonists.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages R5-R7"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90033-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19555808","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":"Stereoselective inhibition of muscarinic receptor subtypes by the eight stereoisomers related to rociverine","authors":"Pascaline Barbier ,&nbsp;Anna R. Renzetti ,&nbsp;Luigi Turbanti ,&nbsp;Cristina Di Bugno ,&nbsp;Francesco Fornai ,&nbsp;Francesca Vaglini ,&nbsp;Roberto Maggio ,&nbsp;Giovanni U. Corsini","doi":"10.1016/0922-4106(95)90024-1","DOIUrl":"10.1016/0922-4106(95)90024-1","url":null,"abstract":"<div><p>The chemical structure corresponding to 1-hydroxy[1,1′-bicyclohexyl]-2-carboxylic acid 2-(diethylamino)-1-methylethyl ester has the classical profile of ester-type antimuscarinic drugs. The presence of three chiral carbons leads to eight stereoisomers and the substitutions on the cyclohexyl ring generate <em>cis</em>-isomers (<strong>1</strong>, named rociverine and <em>trans</em>-isomers (<strong>2</strong>). The aim of this study was to determine the binding pattern of the eight stereoisomers and two derived compounds, (1S,2S)-1-hydroxy[1,1′-bicyclohexyl]-2-carboxylic acid 2-(dimethylamino)-1-ethyl ester (<strong>3</strong>) and (1S,2S)-1-hydroxy[1,1′-bicyclohexyl]-2-carboxylic acid (S)-2-(diethylamino)-1-methylethyl ester methyl iodide (<strong>4</strong>), at the five cloned muscarinic receptors stably expressed in chinese hamster ovary cells, in order to define how stereochemical modifications could affect the affinity. Our data showed that <em>cis</em>-stereoisomers exhibited higher variations in affinity than <em>trans</em>-stereoisomers. Among the <em>cis</em>-stereoisomers, those with the (1R,2R) configuration showed considerably higher affinities (up to 240-fold) than those with the (1S,2S) configuration. The (1S,2S) configuration was important for binding selectivity; this was confirmed also by the use of the two additional compounds.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 125-132"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90024-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19555811","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":"Aldosterone inhibits nitric oxide synthesis in rat vascular smooth muscle cells induced by interleukin-1 β","authors":"Uichi Ikeda ,&nbsp;Toshiko Kanbe ,&nbsp;Ichiro Nakayama ,&nbsp;Yasuhiro Kawahara ,&nbsp;Mitsuhiro Yokoyama ,&nbsp;Kazuyuki Shimada","doi":"10.1016/0922-4106(95)90018-7","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90018-7","url":null,"abstract":"<div><p>We investigated the effects of aldosterone on nitric oxide (NO) synthesis in vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of NO, and the expression of inducible NO synthase mRNA and protein in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1β (10 ng/ml) for 24 h caused a significant increase in nitrite generation. The interleukin-1β-induced nitrite production by vascular smooth muscle cells was significantly inhibited by aldosterone in a dose (10⁻⁹ ∼ 10⁻⁶ M)-dependent manner. Incubation with interleukin-1β for 12 ∼ 24 h caused inducible NO synthase mRNA expression in vascular smooth muscle cells, whereas aldosterone had a suppressive effect on its expression. Aldosterone also decreased interleukin-1β-induced inducible NO synthase protein accumulation. These results indicate that aldosterone inhibits NO synthesis under interleukin-1β-stimulated conditions in vascular smooth muscle cells.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 69-73"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90018-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71783968","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":"Rolipram increases cyclic GMP content in L-arginine-treated cultured bovine aortic endothelial cells","authors":"Thierry Kessler,&nbsp;Claire Lugnier","doi":"10.1016/0922-4106(95)90030-6","DOIUrl":"10.1016/0922-4106(95)90030-6","url":null,"abstract":"<div><p>Cultured bovine aortic endothelial cells only contain two cyclic nucleotide phosphodiesterases isoforms: PDE II (cyclic GMP stimulated) and PDE IV (rolipram sensitive). The effects of cilostamide or rolipram alone or together, on cyclic AMP and cyclic GMP levels, were measured in indomethacin-treated endothelial cells alone or in the presence of nitric oxide (NO) modulators. In all conditions, cyclic AMP levels were potently increased (8–13-fold) only when PDE II and PDE IV inhibitors were given together. Cyclic GMP levels were not modified by these PDE inhibitors in control and N^G-nitro-<span>L</span>-arginine-methyl ester-treated cells. But surprisingly, in <span>L</span>-arginine-treated cells, cyclic GMP content was increased by 42% by rolipram alone, and combination of rolipram with cilostamide resulted in a further increase in cyclic GMP content (to 153% compared to control cells). These results suggest that in presence of the NO synthase substrate (<span>L</span>-arginine), an increase in cyclic AMP level may upregulate the <span>L</span>-arginine/NO/cyclic GMP pathway.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 163-167"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90030-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19555743","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":"Identification of 2-amino-2-methyl-4-phosphonobutanoic acid as an antagonist at the mGlu4a receptor","authors":"Patricia A. Johansen ,&nbsp;Michael B. Robinson","doi":"10.1016/0922-4106(95)90032-2","DOIUrl":"10.1016/0922-4106(95)90032-2","url":null,"abstract":"<div><p>2-Amino-2-methyl-4-phosphonobutanoic acid (MAP4) was tested for interactions with the mGlu_4a receptor which when expressed in baby hamster kidney (BHK570) cells couples to inhibition of forskolin-stimulated cAMP production. MAP4 had no agonist activity at this receptor and caused a concentration-dependent inhibition of the reduction in forskolin-stimulated cyclic AMP formation elicited by L-2-amino-4-phosphonobutanoic acid (L-AP4). Inhibition by MAP4 was consistent with a competitive mechanism of action (Schild slope = 1.2) with a <em>K</em>_i of 190 μM. MAP4 is the first antagonist identified for the mGlu_4a receptor.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages R1-R3"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90032-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19555807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecystokinin and gastrin are not equally sensitive to GTPγS at CCKB receptors: importance of the sulphated tyrosine","authors":"Jean-Christophe Lallement,&nbsp;Catherine Oiry,&nbsp;Ana-Christina Lima-Leite,&nbsp;Marie-Francoise Lignon,&nbsp;Pierre Fulcrand,&nbsp;Jean-Claude Galleyrand,&nbsp;Jean Martinez","doi":"10.1016/0922-4106(95)90017-9","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90017-9","url":null,"abstract":"<div><p>We have shown that gastrin and cholecystokinin octapeptide (CCK-8) are differently coupled to G protein (GTP-binding protein) through type B cholecystokinin receptors in guinea-pig brain membranes and Jurkat cells. Indeed, the gastrin-13 binding affinity is strongly reduced by stable guanyl nucleotides, whereas CCK-8 binding is only slightly affected. In order to determine the structural requirements regulating such coupling, we have synthesized several gastrin and cholecystokinin fragments (sulphated or unsulphated) elongated at the N-terminus of the common C-terminal tetrapeptide. We investigated their interaction with CCK_B receptors in guinea pig brain membranes and Jurkat cells and their involvement in the G protein coupling. Their apparent binding affinities to CCK_B receptors were measured by inhibition of [¹²⁵I]Bolton Hunter-CCK-8 (3-[¹²⁵I]iodo-4-hydroxyphenyl)propionyl-CCK-8) binding in the presence or absence of GTP<em>γ</em>S (guanosine 5′-<em>O</em>-(3-thio)triphosphate) or aluminium tetrafluoride (AlF₄⁻). Activation of the G proteins by GTP<em>γ</em>S or AlF₄⁻ led to a decrease in binding affinity for the gastrin related peptides, the common CCK-gastrin C-terminal forms, the cholecystokinin hexapeptide and the unsulphated cholecystokinin heptapeptide. Sulphated CCK-7, CCK-8, and cionin apparent binding affinities were not affected. These finding indicated that the sulphated tyrosine in position 7 in CCK (as counted from the C-terminus), provides the cholecystokinin selectivity for the CCK_B receptor compared to gastrin. The results are discussed with the aim to better clarify the physiological relevance of gastrin and cholecystokinin toward CCK_B receptors and their related intracellular events.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 61-67"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90017-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71826439","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":"Modulation of Ca2+-activated K+ channel activity by tyrosine kinase inhibitors in vascular smooth muscle cell","authors":"Zhigang Xiong,&nbsp;Ethan Burnette,&nbsp;Donald W. Cheung","doi":"10.1016/0922-4106(95)90023-3","DOIUrl":"10.1016/0922-4106(95)90023-3","url":null,"abstract":"<div><p>The effects of the tyrosine kinase inhibitors genistein, lavendustin A, and tyrphostin A25 on Ca²⁺-activated K⁺ channel activities in freshly isolated single vascular smooth muscle cells from the rat tail artery were studied by patch clamp recording technique. Genistein (5–50 μM) and lavendustin A (10 μM) increased whole-cell Ca²⁺-activated K⁺ channel currents. Increase in single channel activities by genistein and lavendustin A was also observed in excised inside-out patches. Diadzein (15 μM), an inactive analogue of genistein, did not alter channel activities. Tyrphostin A25 (10 nM), which had no significant effect on whole-cell currents in concentrations up to 50 μM, increased the open probability of the channels by 841% in inside-out patches. No potentiation of whole-cell and single channel activities by genistein was observed when ATP was omitted from the intracellular solutions. These observations suggest that tyrosine kinase modulates Ca²⁺-activated K⁺ channel activities in vascular smooth muscle cells.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 117-123"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90023-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19555810","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":"Protection by lazaroids of the erythrocyte (Ca2+, Mg2+)-ATPase against iron-induced inhibition","authors":"Asma Zaidi,&nbsp;Michael C. Marden,&nbsp;Claude Poyart,&nbsp;Liliane Leclerc","doi":"10.1016/0922-4106(95)90025-X","DOIUrl":"10.1016/0922-4106(95)90025-X","url":null,"abstract":"<div><p>The calmodulin-stimulated (Ca²⁺, Mg²⁺)-ATPase (calmodulin-ATPase) of the erythrocyte membrane is susceptible to oxidative stress induced by heme and non-heme iron. There is a time-and concentration-dependent inhibition of the calmodulin-ATPase activity when the erythrocyte membranes are treated with either iron or hemin. In the present study, the calmodulin-ATPase has been used as a model system to evaluate the protective effects of a vitamin E analog (U83836E) and two 21-aminosteroids (U74500A and U74389G) against calmodulin-ATPase inhibition induced by iron and hemin.</p><p>The drugs, lazaroids from Upjohn, can significantly protect the enzyme against iron-induced inhibition and also causes a decrease in the formation of thiobarbituric acid reactive species, with an IC₅₀ of 0.4 μM for the drug U83836E and 4 μM for the drug U74500A. The 21-aminosteroid U74389G does not restore iron-inhibited calmodulin-ATPase activity under similar conditions. At higher concentrations (&gt; 100 <em>μ</em>M) all three drugs inhibit the calmodulin-ATPase activity. None of the drugs tested can restore hemin-inhibited calmodulin-ATPase activity.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 133-139"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90025-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19555812","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":"Erratum to: ‘Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets’ Eur. j. pharmacol. — Mol. pharmacol. sect. 288 (1995) 373–477","authors":"Daiga M. Helmeste ,&nbsp;Siu W. Tang ,&nbsp;Christopher Reist ,&nbsp;Ryan Vu","doi":"10.1016/0922-4106(95)90034-9","DOIUrl":"10.1016/0922-4106(95)90034-9","url":null,"abstract":"<div><p>The serotonin uptake inhibitors sertraline, paroxetine and fluoxetine were compared with imipramine and the calmodulin antagonists <em>N</em>-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) and calmidazolium, for their effects on intracellular Ca²⁺ mobilization in human platelets. All serotonin uptake inhibitors and calmodulin antagonists augmented thrombin-mediated increases in intracellular Ca²⁺. Sertraline, calmidazolium and W-7 also caused large dose-dependent increases in baseline levels of intracellular Ca²⁺. There was a rough correlation between the ability to elevate intracellular Ca²⁺ and potencies for inhibition of calmodulin. Neomycin, an inhibitor of inositol trisphosphate (IP₃) generation, significantly inhibited the effects of sertaline. This is consistent with a role of IP₃ and calmodulin in the effects of these drugs.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 173-174"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90034-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"53949161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding of distamycin and chromomycin to human immunodeficiency type 1 virus DNA: a non-radiactive automated footprinting study","authors":"Giordana Feriotto,&nbsp;Carlo Mischiati,&nbsp;Nicoletta Bianchi,&nbsp;Marco Passadore,&nbsp;Roberto Gambari","doi":"10.1016/0922-4106(95)90020-9","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90020-9","url":null,"abstract":"<div><p>Sequence-selectivity of DNA-binding drugs was recently reported in a number of studies employing footprinting and gel retardation approaches. In this paper we studied sequence-selectivity of the binding of chromomycin and distamycin to DNA by performing DNase I footprinting and analysis of the cleaved fragments by the Pharmacia ALF^TM DNA Sequencing System. As a model system we employed the long terminal repeat of the human immunodeficiency type 1 virus. The main conclusion of our experiments is that automated analysis of DNase I footprinting is a fast and reliable technique to study drugs-DNA interactions. The results obtained suggest that distamycin and chromomycin differentially interact with the long terminal repeat of the human immunodeficiency type 1 virus; this differential binding depends upon the DNA sequences recognized. The data presented are consistent with a preferential binding of distamycin to DNA sequences of the binding sites of nuclear factor kappa B and transcription factor IID. By contrast, distamycin exhibits only weak binding to DNA sequences recognized by the promoter-specific transcription factor Sp1. Unlike distamycin, chromomycin preferentially interacts with the binding sites of the promoter-specific transcription factor Sp1.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"290 2","pages":"Pages 85-93"},"PeriodicalIF":0.0,"publicationDate":"1995-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90020-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71826437","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}