European Journal of Pharmacology: Molecular Pharmacology最新文献

{"title":"Effects of channel modulation and pH on IsK inhibition by the novel class III antiarrhythmic azimilide (NE-10064)","authors":"Tobias Herzer ,&nbsp;Carsten A. Wagner ,&nbsp;Siegfried Waldegger,&nbsp;Florian Lang,&nbsp;Andreas E. Busch","doi":"10.1016/0922-4106(95)90144-2","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90144-2","url":null,"abstract":"<div><p>Inhibition of human I_sK channels expressed in <em>Xenopus</em> oocytes by the novel class III antiarrhythmic azimilide was studied under distinct treatments known to increase I_sK (hypotonic solution, A23187 and isoproterenol). Azimilide inhibited I_sK under all conditions with similar potency. Reduction of ionic strength or pH changes from pH 6.5 to 8.5 did not alter I_sK amplitude. However, inhibition of I_sK by azimilide was decreased by reduced pH, but not by reduced ionic strength. Further, the apparent affinity of azimilide was increased more than tenfold by increasing pH from 6.5 to 8.5. The data suggest that the neutral form of azimilide, a weak base, inhibits I_sK via a lipophilic protein-drug interaction. pH-dependence of azimilide may significantly alter its effects on I_sK under distinct pathophysiological conditions (acidosis vs. alkalosis) and in distinct locations (heart vs. kidney).</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 205-208"},"PeriodicalIF":0.0,"publicationDate":"1995-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90144-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71780039","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":"Involvement of cyclic AMP in the effects of phosphodiesterase IV inhibitors on arachidonate release from mononuclear cells","authors":"Aziz Hichami ,&nbsp;Elisabeth Boichot ,&nbsp;Noëlla Germain ,&nbsp;Alain Legrand ,&nbsp;Indres Moodley ,&nbsp;Vincent Lagente","doi":"10.1016/0922-4106(95)90129-9","DOIUrl":"10.1016/0922-4106(95)90129-9","url":null,"abstract":"<div><p>The effects of selective phosphodiesterase inhibitors, cyclic AMP (cAMP) elevating agents and stable analogues of cyclic nucleotides, on the release of arachidonate induced by N-formyl-Met-Leu-Phe (fMLP) were investigated on human peripheral blood mononuclear cells. The selective phosphodiesterase IV inhibitors, rolipram and Ro 20–1724, and the non-selective phosphodiesterase inhibitor, theophylline, elicited a concentration-dependent inhibition of arachidonate release (EC₅₀ = 1.3 × 10⁻⁶ M, 3.2 × 10⁶⁻ M and 3.7 × 10⁻⁴ M respectively). The selective phosphodiesterase III inhibitor, milrinone (10⁻⁵ M), only caused a slight effect while the phosphodisterese V inhibitor, zaprinast (10⁻⁵ M), the <em>β</em>₂-adrenoceptor agonists, salbutamool and fenoterol (10⁻⁵ M), failed to inhibit arachidonate release. Forskolin (10⁻⁵ M) and N⁶,2′-O-dibutyryladenosien 3′:5′cyclic monophosphate (db-cAMP, 10⁻³ M) elicited a moderate inhibition. Forskolin increased the effects of rolipram and Ro 20–1724 (EC₅₀ = 4.5 × 10⁻⁷ M and 4 × 10⁻⁷M respectively). Incubation of the cells with rolipram (10⁻⁸ to 10⁻⁵ M), Ro 20–1724 (10⁻⁸ to 10⁻⁵ M), forskolin (10⁻⁵ M) or salbutamol (10⁻⁵ M) alone, induced a moderate increase or no increase at all in intrecellular cAMP. However, in the presence of forskolin, rolipram (10⁻⁸ to 10⁻⁶M) and Ro 20–1724 (10⁻⁸ to 10⁻⁶M) induced a significant and concentration-dependent increase in intracellular levels of cAMP. These results suggest that the potent inhibition of arachidonate release from mononuclear cells by selective phosphodiesterase IV inhibitors may be due to increases in discrete pools of intracellular cAMP.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 91-97"},"PeriodicalIF":0.0,"publicationDate":"1995-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90129-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19546939","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":"Lipid A and the lipid A analogue anti-tumour compound ONO-4007 induce nitric oxide synthese in vitro and in vivo","authors":"Yoshiyuki Hattori ,&nbsp;Csaba Szabó ,&nbsp;Steven S. Gross ,&nbsp;Christoph Thiemermann,&nbsp;John R. Vane","doi":"10.1016/0922-4106(95)90128-0","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90128-0","url":null,"abstract":"<div><p>The ability of lipid A and the antitumour compound, ONO-4007 (sodium2-deoxy-2-[3S-(9-phenylnonanoyloxy)tetradecanoyl]amino-3-O-(9phenylnonanoyl)-D- glucopyranose 4-sulphate) to induce nitric oxide (NO) synthase was investigated in vitro and in vivo, in comparison to the effects of lipopolysacchride and di-and monophosphoryl lipid A. In J774.2 macrophages, lipopolysaccharide, di-and monophosphoryl lipid A and ONO-4007 (10⁻⁹-10⁻⁵ g/ml) alone, or in combination with interferion-γ, induced NO synthese (order of potency: lipopolysaccharide &gt; diphosphoryl lipid A &gt; monophosphoryl lipid A &gt; ONO-4007). ONO-4007 increased the activity of the inducible NO synthase in the lung of anesthetised rats (20% of the increase caused by bacterial lipopolysaccharide). Thus, ONO-4007 is a weak inducer of the inducible isoform of NO synthase in vitro and in vivo. The finding that di-and monophosphoryl lipid A also induce NO synthase indicates that the lipid A moiety of lipopolysaccharide contributes to the induction of NO synthase by lipopolysaccharide. The induction of NO synthase by ONO-4007, resulting in the formation of cytotoxic NO may contibute to the antitumour activity of the compound.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 83-90"},"PeriodicalIF":0.0,"publicationDate":"1995-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90128-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71779243","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":"Ketanserin and ritanserin discriminate between recombinant human 5-HT1Dα and 5-HT1Dβ receptor subtypes","authors":"John M. Zgombick,&nbsp;Lee E. Schechter ,&nbsp;Stefan A. Kucharewicz,&nbsp;Richard L. Weinshank,&nbsp;Theresa A. Branchek","doi":"10.1016/0922-4106(95)90183-3","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90183-3","url":null,"abstract":"<div><p>Compounds able to discriminate functionally between the closely related cloned human 5-HT_1Dα and 5-HT_1Dβ receptor subtypes have not been reported previously. In [³H]5-HT competition assays, the classical 5-HT_2A receptor antagonists, ritanserin and ketanserin, displayed moderate affinity (p<em>K</em>_i = 7.30 and 7.17, respectively) and marked selectivity (22-and 71-fold, respectively) for the recombinant human 5-HT_1Dα subtype relative to the 5-HT_1Dβ receptor. In contrast, the nonselective 5-HT_{<span><math><mtext>1</mtext><mtext>2</mtext></math></span>} receptor antagonist, methiothepin, exhibited similar binding affinities (p<em>K</em>_i=7.64−8.01) for both recombinant 5-HT_1D subtypes. The antagonistic properties of these compounds were evaluated for their ability to block 5-HT-induced inhibition of forskolin-stimulated cAMP accumulation in intact cells stably expressing either 5-HT_1Dα or 5-HT_1Dβ receptors. All three compounds behaved as antagonists devoid of intrinsic activity in the functional assays. The apparent p<em>K</em>_b values determined in functional assays closely matched their p<em>K</em>_i values obtained in binding assays. Since ketanserin exhibits significant selectivity for the human 5-HT_1Dα receptor, this antagonist can be used as a pharmacological tool to discriminate between 5-HT_1Dα and 5-HT_1Dβ receptor-mediated responses in human tissues.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 1","pages":"Pages 9-15"},"PeriodicalIF":0.0,"publicationDate":"1995-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90183-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71868934","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":"Endothelin-1, but not endothelin-3, suppresses lipoprotein lipase gene expression in brown adipocytes differentiated in culture","authors":"Yoko Uchida,&nbsp;Kaoru Irie,&nbsp;Fujiko Tsukahara,&nbsp;Ken-ichi Ohba,&nbsp;Akira Ogawa,&nbsp;Emiko Fujii,&nbsp;Takamura Muraki","doi":"10.1016/0922-4106(95)90186-8","DOIUrl":"10.1016/0922-4106(95)90186-8","url":null,"abstract":"<div><p>The effect of endothelins on lipoprotein lipase activity and lipoprotein lipase mRNA levels was studied in brown adipocytes differentiated in culture. Lipoprotein lipase activity was determined in two fractions; lipoprotein lipase released by heparin (10 IU/ml, 1 h) into the medium (heparin-releasable fraction) and lipoprotein lipase activity remaining in cells (extractable table). Time-course studies showed that endothelin-1 (10⁻⁷ M) progressively decreased both lipoprotein lipase fractions (heparin-releasable, extractable), until nadir at 24 h. Endothelin-1 reduced both lipoprotein lipase activities (heparin-releasable, extractable) in a concentration-dependent manner, whereas endothelin-3 did not produce any significant changes in either of them. Northern blot analysis revealed that endothelin-1 (10⁻⁷−10⁻¹¹ M) caused a concentration-dependent decrease in lipoprotein lipase mRNA obtained from cells on day 9. Furthermore, pretreatment of brown adipocytes with endothelin <span>ETA</span> receptor antagonist FR139317 antagonized the endothelin-1-induced reduction of lipoprotein lipase activity and lipoprotein lipase mRNA. These results suggest that endothelin-1 decreases lipoprotein lipase activity by inhibiting the lipoprotein lipase gene expression in brown adipocytes differentiated in culture, possibly through endothelin ETA receptors on cell membranes. Because of marked reduction of lipoprotein lipase activity and its mRNA as a marker of adipogenic differentiation, endothelin-1 may have an inhibitory role in the differentiation of brown adipocytes.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 1","pages":"Pages 33-41"},"PeriodicalIF":0.0,"publicationDate":"1995-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90186-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19531556","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 human neutrophil function by tolfenamic acid involves inhibition of Ca2+ influx","authors":"Hannu Kankaanranta ,&nbsp;Heikki Wuorela ,&nbsp;Elise Siltaloppi ,&nbsp;Pauli Vuorinen ,&nbsp;Heikki Vapaatalo ,&nbsp;Eeva Moilanen","doi":"10.1016/0922-4106(95)90184-1","DOIUrl":"10.1016/0922-4106(95)90184-1","url":null,"abstract":"<div><p>The present work was designed to study the pharmacological control of the receptor-mediated activation of human neutrophils by tolfenamic acid (2-[(3-chloro-2-methylphenyl)-amino]benzoic acid). Tolfenamic acid inhibited in a concentration-dependent manner the degranulation response and Ca²⁺ influx in neutrophils activated either by the chemotactic peptide fMLP (<em>N</em>-formyl-methionyl-leucylphenylalanine) or Ca²⁺ ionophore A23187 (calcimycin). When fMLP was used to activate neutrophils, tolfenamic acid (30 μM) reduced Ca²⁺ influx by 50% and degranulation by 20%. A23187-triggered Ca²⁺ influx and degranulation were inhibited by 60% and 40%, respectively, by 30 μM tolfenamic acid. Tolfenamic acid did not inhibit the release of Ca²⁺ from intracellular stores induced either by fMLP or A23187. To confirm the inhibition of receptor-mediated cation influx by tolfenamic acid, the agonist induced Mn²⁺ influx was studied in Ca²⁺ free medium. Tolfenamic acid (10–30 μM) reduced fMLP-stimulated Mn²⁺ influx in neutrophils in a concentration-dependent manner. The simultaneous Ca²⁺ release from intracellular stores was not affected. Protein kinase C activity in sonicated human neutrophils and the purified enzyme from rat brain were inhibited by the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) but not by tolfenamic acid. Both failed to inhibit neutrophil degranulation induced by phorbol myristate acetate, a protein kinase C activator. Tolfenamic acid (100 μM) increased the cellular cAMP levels up to 1.3-fold in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. No effects on cellular cGMP levels were found. In conclusion, tolfenamic acid inhibits both fMLP-and Ca²⁺-ionophore induced Ca²⁺ influx in human neutrophils concomitantly with its inhibitory action on degranulation. This suggests that the inhibitory action of tolfenamic acid on human neutrophil functions is mediated by a mechanism involving inhibition of Ca²⁺ influx. Neither protein kinase C nor cyclic nucleotides seem to have a major role in the inhibitory action of tolfenamic acid on human neutrophil functions.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 1","pages":"Pages 17-25"},"PeriodicalIF":0.0,"publicationDate":"1995-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90184-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19531554","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":"Expression and characterization of the substance P (NK1) receptor in the rat pituitary and AtT20 mouse pituitary tumor cells","authors":"Anett Winkler,&nbsp;Gisela Papsdorf,&nbsp;Jutta Odarjuk,&nbsp;Wolf-Eberhard Siems,&nbsp;Jörns Fickel,&nbsp;Matthias F. Melzig","doi":"10.1016/0922-4106(95)90188-4","DOIUrl":"10.1016/0922-4106(95)90188-4","url":null,"abstract":"<div><p>Although substance P is known to take part in the regulation of the anterior pituitary, no conclusive evidence for the expression of the tachykinin NK₁ receptor has been found yet in the pituitary or pituitary derived cells. With the reverse transcription-polymerase chain reaction (RT-PCR) method we could detect the low abundant transcripts of the NK₁ receptor in the rat pituitary and in the AtT20 cell line (clone D16v). Furthermore, the functional expression of the NK₁ receptor in AtT20 cells was confirmed by activation of the phosphatidylinositol-calcium second messenger system when the cells were treated with substance P. In addition, binding studies also indicated the functional expression of this receptor in AtT20 cells. Thus we provide the first evidence that the NK₁ receptor is expressed in AtT20 cells and the rat pituitary.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 1","pages":"Pages 51-55"},"PeriodicalIF":0.0,"publicationDate":"1995-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90188-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19531558","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":"Effects of protein kinase A activation on endothelin- and ATP-induced signal transduction","authors":"Wan Wan Lin","doi":"10.1016/0922-4106(95)90182-5","DOIUrl":"10.1016/0922-4106(95)90182-5","url":null,"abstract":"<div><p>C₆ glioma cells possess endothelin ET_A receptor and P₂ purinoceptor coupled to two signaling pathways, i.e. phosphoinositide turnover and inhibition of adenylyl cyclase. In this study, the effects of raising cyclic AMP levels on the inositol phospholipid hydrolysis and adenylyl cyclase inhibition caused by endothelin-1 and ATP in C₆ glioma cells were examined. Pretreatment with cAMP generating agents (forskolin, isoproterenol and cholera toxin) or dibutyryl cAMP for 10 min-3 h did not affect the inositol phosphate accumulation caused by endothelin and ATP. Long-term (8–24 h) pretreatment with isoproterenol, forskolin, cholera toxin or dibutyryl cAMP resulted in a 40–50% inhibition of endothelin- and ATP-stimulated inositol phosphate accumulation, whereas the EC₅₀ values of endothelin and ATP were not affected. Consistent with the effects on endothelin and ATP, NaF-induced inositol phosphate formation was also inhibited by cAMP generating agents to a similar extent. Permeabilized cells from 24 h isoproterenol-or forskolin-pretreated C₆ cells also showed a diminished Ca²⁺-sensitivity of phosphoinositide-specific phospholipase C and also attenuated the potentiation response caused by GTPγS. The inhibitory effects on adenylyl cyclase by endothelin, ATP and 2-methylthio-ATP were unaffected by 24 h pretreatment with isoproterenol or forskolin. Long-term treatment with dibutyryl cGMP did not affect the two signaling pathways caused by ATP and endothelin. It is concluded that the phosphoinositide turnover, but not the adenylyl cyclase inhibition caused by endothelin and ATP in C₆ cells, was inhibited by protein kinase A-dependent pathway. The decreased phospholipase C activity is responsible for the inhibitory effect of protein kinase A-dependent pathway on agonist-induced phosphoinositide turnover in C₆ glioma cells.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 1","pages":"Pages 1-7"},"PeriodicalIF":0.0,"publicationDate":"1995-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90182-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19529709","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":"Anti-oxidant actions of oxymethazoline and xylomethazoline","authors":"Gerrit-Jan Westerveld ,&nbsp;Robert A. Scheeren ,&nbsp;Ingrid Dekker ,&nbsp;Désirée H. Griffionen ,&nbsp;Hans-Peter Voss ,&nbsp;Aalt Bast","doi":"10.1016/0922-4106(95)90185-X","DOIUrl":"10.1016/0922-4106(95)90185-X","url":null,"abstract":"<div><p>Anti-oxidant actions of oxymethazoline and xylomethazoline were investigated by measuring inhibition io microsomal lipid peroxidation and hydroxyl radical scavenging activity. Oxymethazoline was shown to be potent inhibitir of lipid peroxidation (IC₅₀ = 4.9 <em>μ</em>M at <em>t</em> = 15 min, IC₅₀ = 81. <em>μ</em>M at <em>t</em> = 30 min), in contrast to xylomethazoline. Both compounds were excellent hydroxyl radical scavengers. Their rate constants (<em>k</em>_S = 1.1 × 10¹² M⁻¹s⁻¹ for oxymethozoline and <em>k</em>_S = 4.7 × 10¹⁰ M⁻¹s⁻¹ for xylomethazoline) exceeded the rate constant of a known powerful scavenger cimetidine (<em>k</em>_S = 1.8 × 10¹⁰ M⁻¹S⁻¹). The difference in inhibiting lipid peroxidation might be explained by the fact that only oxymethazoline has a hydroxy group which can donate a hydrogen atom and terminate the chain reaction of lipid peroxidation. The mechanism of hydroxyl radical scavenging activity is still unclear. Moreover oxymethazoline seems to have a different mode of action in scavenging hydroxyl radicals than oxylomethazoline and cimetidine which results in an extremely high rate constant. Because oxidants play a role in tissue damage in inflammation, it was hypothesized that especially oxymethazoline and to a lesser extent xylomethazoline may have an additional beneficial effect, due to their anti-oxidant properties, in the topical treatment of nasal inflammation.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 1","pages":"Pages 27-31"},"PeriodicalIF":0.0,"publicationDate":"1995-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90185-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19531555","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":"Dual effect of muscarinic receptor agonists on Ca2+ mobilization in SH-SY5Y neuroblastoma cells","authors":"Jaak Järv ,&nbsp;Rasmus Hautala ,&nbsp;Karl E.O. Åkerman","doi":"10.1016/0922-4106(95)90187-6","DOIUrl":"10.1016/0922-4106(95)90187-6","url":null,"abstract":"<div><p>The muscarinic receptor-stimulated mobilisation of calcium ions in SH-SY5Y neuroblastoma cells was measured as function of the concentration of seven muscarinic receptor agonists and partial agonists: carbamoylcholine, acetylcholine, propionylcholine, butyrylcholine, acetylthiocholine, methylfurmethide and tetrametylammonium. The dose-response curves reached a clear maximum followed by a downturn of the curve. The concentration interval where the activatory and inhibitory effects occured depended on the structure of the ligand. The bell-shaped dose-response curves were analysed assuming that the drugs interact with two sites, which are responsible for agonistic and antagonistic effects, on the muscarinic receptors. The results indicate that full vs. partial agonism is at least in part determined by relative affinities of these two sites.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 1","pages":"Pages 43-50"},"PeriodicalIF":0.0,"publicationDate":"1995-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90187-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19531557","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}