European Journal of Pharmacology: Molecular Pharmacology最新文献

{"title":"Bradykinin receptors and signal transduction pathways in peritoneal guinea pig macrophages","authors":"Sabine Böckmann ,&nbsp;Inge Paegelow","doi":"10.1016/0922-4106(95)90138-8","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90138-8","url":null,"abstract":"<div><p>The presence of a bradykinin receptor on guinea pig peritoneal macrophages was evidenced by binding studies and by the effect of bradykinin on activation of the phospholipase C and the increase in intracellular calcium concentration ([Ca²⁺]_i). Binding studies demonstrated a specific, saturable binding for [³H]bradykinin inhibited by the bradykinin B₂ (HOE 140) but not bradykinin B₁ (des-Arg⁹[Leu⁸]bradykinin) receptor antagonist. Scatchard analysis revealed a single class of B₂ bradykinin binding sites with a binding affinity (k_d) of 0.8 nM and a receptor concentration (<em>B</em>_max) of 35 fmol/5 × 10⁶ cells, representing approximately 4000 bradykinin receptors per cell. Kinetic studies confirmed the presence of this single binding site by the determination of similar binding affinity. Activation of peritoneal macrophages by bradykinin resulted in a time-and dose-dependent release of inositol phosphates determined by anion exchang chromatography and intracellular calcium analyzed using fura-2/AM. The increase in [Ca²⁺]_i induced by bradykinin was blocked by the specific bradykinin B₂ receptor antagonist HOE 140 but not by the bradykinin B₁ receptor antagonist des-Arg⁹[ These studies provide novel information regarding the nature of kinin receptors on guinea pig peritoneal macrophages and their signal transduction pathways.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 159-165"},"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)90138-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71780038","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":"Receptor-induced heterologous desensitization of receptor-regulated phospholipase C","authors":"Marie-Christine Galas,&nbsp;T.Kendall Harden","doi":"10.1016/0922-4106(95)90140-X","DOIUrl":"10.1016/0922-4106(95)90140-X","url":null,"abstract":"<div><p>Activation of the P_2Y purinoceptor on turkey erythrocytes results in a G₁₁-mediated activation of a phospholipase C-β isoenzyme and hydrolysis of polyphosphoinositides. The role of the protein kinase C and Ca²⁺-mobilizing arms of the inositol lipid signalling cascade in P_2Y purinoceptor-induced desensitization of phospholipase C has been examined using erythrocytes as a model system. Preincubation of intact erythrocytes with either the P_2Y purinoceptor agonist, ADPβS, or the protein kinase C-activating phorbol ester, phorbol 12-myristate, 13 acetate (PMA), resulted in a time of preincubation-dependent decrease in guanine nucleotide-, P_2Y purinoceptor-, and β-adrenoceptor-stimulated phospholipase C activities in membranes isolated from these cells. The extent of heterologous desensitization induced by ADPβS and PMA were additive suggesting that they did not share a common mechanism. A lack of involvement of activation of protein kinase C in P_2Y purinoceptor-induced heterologous desensitization was further supported by the observation that although protein kinase C inhibitors or down-regulation of protein kinase C resulted in a loss of PMA-induced desensitization, neither treatment affected the extent of P_2Y purinoceptor-induced desensitization. In addition, elevation of intracellular Ca²⁺ or prevention of its elevation did not induce heterologous desensitization and had no effect on the desensitization induced by ADPβS. Thus, neither the protein kinase C nor Ca²⁺ mobilizing arms of the inositol lipid signaling pathway appear to be involved in P_2Y purinoceptor promoted heterologous desensitization of phospholipase C. These results are consistent with the existence of a novel feedback pathway for agonist-induced heterologous desensitization of a second messenger generating enzyme. Preincubation of cells with ADPβS or the β-adrenoceptor agonist, isoproterenol, followed by rechallenge with each of the receptor agonist revealed that receptor-specific desentization occurs in addition to heterologous desensitization. Thus, multiple mechanisms account for agonist-induced desentization of the inositol lipid signalling system of turkey erythrocytes.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 175-182"},"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)90140-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19547031","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":"Role of opioid peptides in the regulation of DNA synthesis in immature rat uterus","authors":"Zsuzsanna Vértes ,&nbsp;Józef L. Környei ,&nbsp;Sándor Kovács ,&nbsp;Marietta Vértes","doi":"10.1016/0922-4106(95)90132-9","DOIUrl":"10.1016/0922-4106(95)90132-9","url":null,"abstract":"<div><p>The effects of a single dose of naloxone and of [D-Met², Pro⁵]enkephalinamide on the DNA synthesis in the uterus of 7, 14 and 21-day-old rat were studied. After [D-Met²,Pro⁵]enkephalinamide treatment, an age-dependent decrease in in vitro [³H]thymidine incorporation into DNA was observed in all studied age groups. In the 21-day-old age group a reduced rate of DNA synthesis was detected for 12 h after [D-Met²,Pro⁵]enkephalinamide treatment followed by the return to control values at 24 h. The rate of inhibition was more marked in the younger age groups. The effect of [D--Met²,Pro⁵]enkephalinamide treatment was completely prevented by the opioid antagonist naloxone injected 30 min prior to the agonist treatment. Naloxone itself resulted in an increase in uterine DNA synthesis. This effect was also more pronounced in younger animals. Specific [³H]naloxone binding was detected both in membrane and nuclear fractions of uterine homogenates. While no age-related changes in binding affinities were found, the number of binding sites varied characteristically during development. Our data suggest the novel involvement of opioid peptides and their receptors in the regulation of uterine development.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 115-120"},"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)90132-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19545910","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":"Potentiation of glucocorticoid-mediated gene expression by the novel benzoquinone derivative (2E)-3-[5-(2,3-dimethoxy-o-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propenoic acid (E3330)","authors":"Hirotoshi Tanaka ,&nbsp;Yuichi Makino ,&nbsp;Masaki Hiramoto ,&nbsp;Hiroshi Handa ,&nbsp;Isao Makino","doi":"10.1016/0922-4106(95)90133-7","DOIUrl":"10.1016/0922-4106(95)90133-7","url":null,"abstract":"<div><p>We examined the effects of the novel benzoquinone derivative (2E-3-[5-(2,3-dimethoxy-<em>o</em>-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid, E3330, on the functional activity of the glucocorticoid receptors. For that purpose we used a cloned CHOpMTGR cells, in which human glucocorticoid receptor cDNA was stably transfected and glucocorticoid receptor was expressed at high levels. After treatment of CHOpMTGR cells with E3330, neither the ligand binding activity nor immunoreactivity of the glucocorticoid receptor was affected. Moreover, E3330 did not affect the sequence-specific DNA binding activity of partially-purified glucocorticoid receptor in vitro. However, a glucocorticoid-inducible promoter was activated by E3330 in a dose-dependent fashion in the presence of the synthetic ligand dexamethasone. Interestingly, E3330 increased nuclear translocation of the glucocorticoid receptor in a ligand-independent fashion, indicating that E3330, through facilitation of the translocation of the glucocorticoid receptor, augments glucocorticoid-mediated gene transcription.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 121-127"},"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)90133-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19545911","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":"Mystixin-7 and mystixin-11 increase cytosolic free Ca2+ and inositol trisphosphates in human A-431 cells","authors":"Juliann Gong Kiang","doi":"10.1016/0922-4106(95)90131-0","DOIUrl":"10.1016/0922-4106(95)90131-0","url":null,"abstract":"<div><p>Mystixin-7 and mystixin-11, small peptides structurally related to corticotropin-releasing factor (CRF), have been shown to attenuate vascular leakage in injured skin. The goal of this study was to characterize changes in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in human epidermoid A-431 cells treated with these two peptides and to investigate the mechanisms by which these changes occurred. The resting [Ca²⁺]_i in A-431 cells at 37°C was 76±2 nM (<em>n</em> = 373). When cells were treated with either peptide, [Ca²⁺]_i increased immediately. The increase depended on the peptide concentration, with a median effective concentration of 299 ± 9 pM for mystixin-7 and 2.23 ± 0.04 pM for mystixin-11. The increases also depended on extracellular Ca²⁺ and were blocked by Cd²⁺, Co²⁺, verapamil, and nifedipine. α-Helical CRF-(9–41), a synthetic CRF receptor antagonist, and pertussis toxin also blocked the increase in [Ca²⁺]_i induced by the two peptides. Taken together, these results suggest that mystixin-7 and mystixin-11 interact with CRF receptors to activate pertussis-sensitive G proteins coupled to L-type Ca²⁺ channels that allow an uptake of extracellular Ca²⁺. Because U-73122, an inhibitor of 1,4,5-inositol trisphosphate production, partially inhibited the increase in [Ca²⁺]_i, we measured inositol trisphosphates in cells stimulated by the two peptides. Both increased inositol triphosphate levels within 1 min. The increase was inhibited by the removal of extracellular Ca²⁺ or treatment with U-73122. The results suggest that the Ca²⁺ influx stimulated by mystixin-11 induces an increase in inositol trisphosphates, resulting in a mobilization of Ca²⁺ from 1,4,5-inositol trisphosphate-sensitive Ca²⁺ pools.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 107-113"},"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)90131-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19546022","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-calmodulin potency of indol alkaloids in in vitro systems","authors":"Attila Molnár,&nbsp;Károly Liliom,&nbsp;Ferenc Orosz,&nbsp;Beáta G. Vértessy,&nbsp;Judit Ovádi","doi":"10.1016/0922-4106(95)90127-2","DOIUrl":"10.1016/0922-4106(95)90127-2","url":null,"abstract":"<div><p>We have demonstrated that bis-indol <em>Vinca</em> alkaloids of anti-mitotic activities (vinblastine, vincristine and navelbine) bind to calmodulin in a Ca²⁺-dependent manner. We designed direct binding tests (flourescence energy transfer and circular dichroism measurements) to quantify the interactions of bis-indol derivatives with calmodulin. The dissociation constants of calmodulin-navelbine and calmodulin-vinblastine complexes with 1:1 stoichiometry are 0.5 μM and 3 μM, respectively. These values indicate that the binding affinities of these <em>Vinca</em> alkaloids to calmodulin and tubulin are comparable. Immunological, enzyme kinetic and fluorescence anisotropy measurements showed that bis-indol alkaloids inhibit the interactions of calmodulin with target proteins. The results of indirect enzyme-linked immunosorbent assay showed that bis-indol alkaloids effectively antagonize with anti-calmodulin antibody for calmodulin binding (IC₅₀ = 90 <em>μ</em>M and 430 <em>μ</em>M for navelbine, vincristine and vinblastine, respectively). According to the fluorescence anisotropy and enzyme kinetic measurements, vinblastine, vincristine and navelbine, similarly to trifluoperazine, the classica calmodulin antagonist, compete with target enzyme [phosphofructokinase (ATP: <span>D</span>-fructose 6-phosphate 1-phosphotransferase, EC 2.7.1.11)] for calmodulin binding and inhibit the calmodulin-mediated inactivation of the enzyme. Monomers, catharantine and vindoline, do not have an inhibitory effect either on immunocomplex formation or on calmodulin-enzyme interaction. Navelbine appeared in our tests as the most potent drug in inhibiting the association of calmodulin to target proteins in comparison to other bis-indol derivatives. Since navelbine and vinblastine posses identical vindoline moiety, although they differ in the catharantine part, the difference in anti-calmodulin potencies is suggested to reside predominantly on this portion of the molecules. These findings might establish the pharmacological importance of these activities in the specificity and toxicity of the drugs.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 73-82"},"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)90127-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19546937","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":"Allosteric modulation of [3H]flunitrazepam binding to recombinant GABAA receptors","authors":"Astrid Slany,&nbsp;Jürgen Zezula,&nbsp;Karoline Fuchs,&nbsp;Werner Sieghart","doi":"10.1016/0922-4106(95)90130-2","DOIUrl":"10.1016/0922-4106(95)90130-2","url":null,"abstract":"<div><p>The allosteric modulation of [³H]flunitrazepam binding by γ-aminobutyric acid (GABA), pentobarbital, (+)-etomidate, etazolate, alphaxalone, propofol and chlormethiazole was investigated in cerebellar membranes from human embryonic kidney (HEK) 293 cells transfected with α₁β₃γ₂ or α₁γ₂ subunits. Results obtained indicate that [³H]flunitrazepam binding to recombinant GABA_A receptors consisting of α₁β₃γ₂ subunits could be modulated by these compounds in a way and with a potency similar to that observed in cerebellar membranes. In addition, it was demonstrated that not only receptors consisting of α₁β₃γ₂, but also those consisting of α₁γ₂ subunits exhibited [³H]flunitrazepam binding which could be stimulated by GABA. In contrast to α₁β₃γ₂ receptors, however, [³H]flunitrazepam binding to recombinant α₁γ₂ receptors was inhibited by pentobarbital, (+)-etomidate, etazolate, alphaxalone, propofol and chlormethiazole. This seems to indicate that binding sites for these compounds are present on α₁γ₂ receptors, but that their allosteric interaction with [³H]flunitrazepam binding sites is different from that of α₁β₃γ₂ receptors.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 99-105"},"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)90130-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19546940","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":"The inositol phosphate response to thrombin in rat right atria differs from the response to noradrenaline","authors":"Elizabeth A. Woodcock,&nbsp;Kim A. Lambert","doi":"10.1016/0922-4106(95)90146-9","DOIUrl":"10.1016/0922-4106(95)90146-9","url":null,"abstract":"<div><p>Addition of thrombin to isolated [³H]inositol-labelled rat right atria stimulated the release of ³H-labelled inositol phosphates. The thrombin response was smaller than the response to noradrenaline and generated a different spectrum of inositol phosphates. Unlike the inositol phosphate response to noradrenaline, the thrombin response was inhibited by pertussis toxin treatment and by the phospholipase C inhibitor U-73122 (1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2 ,5-dione). The data indicate that the thrombin stimulation involves different G-proteins and phospholipase C isoforms from those which couple <em>α</em>₁-adrenoceptors in the myocardium.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 213-216"},"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)90146-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19547037","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":"Deriving the therapeutic concentrations for clozapine and haloperidol: The apparent dissociation constant of a neuroleptic at the dopamine D2 or D4 receptor varies with the affinity of the competing radioligand","authors":"Philip Seeman ,&nbsp;Hubert H.M. Van Tol","doi":"10.1016/0922-4106(95)90125-6","DOIUrl":"10.1016/0922-4106(95)90125-6","url":null,"abstract":"<div><p>The apparent dissociation constant, <em>K</em>_i, for a neuroleptic at the dopamine D₂ or D₄ receptor was consistently higher when competed against [³H]nemonapride than against [³H]spiperone which was in turn higher than that against [³H]raclopride. This finding obtained for all four types of dopamine receptors studied, including the native dopamine D₂ receptor in the anterior pituitary tissue, the human D_2long receptor, the human D_2short receptor and the human D_4.4 receptor. Some neuroleptics revealed a difference of over 10-fold between the <em>K</em>_i using [³H]nemonapride and the <em>K</em>_i using [³H]raclopride. The <em>K</em>_D values of the three ³H-ligands and the neuroleptic <em>K</em>_i values were lower when using a much lower concentration of tissue, indicating that depletion of ligand presumably accounted for the phenomenon. The <em>K</em>_i values of each neuroleptic were related to the the tissue/buffer partition coefficients of the three ³H-ligands. Extrapolating the neuroleptic <em>K</em>_i value down to a tissue/buffer partition coefficient of unity or zero led to a <em>K</em>_i value for competition versus a water-soluble ligand such as dopamine. Clozapine extrapolated to a <em>K</em>_i value of 1.3 nM. Direct measurement gave a <em>K</em>_i value of 1.6 nM for [³H]clozapine at the dopamine D₄ receptor. When competing versus endogenous dopamine, this clozapine value of 1.6 nM would rise to 20 nM for the blockade of 75% of dopamine D₄ receptors, matching the observed therapeutic concentration of 18 nM. These data also explain why clozapine occupies 48% of the D₂ receptors in patients when measured with [¹¹C]raclopride, but between 0% and 22% when measured with [¹⁸F]methylspiperone or [¹⁸F]fluoroethylspiperone.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 59-66"},"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)90125-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19546935","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":"Ca2+-activated outward-rectifier K+ channels and histamine release by rat gastric enterochromaffin-like cells","authors":"Hideki Sakai ,&nbsp;Yoshiaki Tabuchi ,&nbsp;Bunpei Kakinoki ,&nbsp;Hisayuki Seike ,&nbsp;Shigeyo Kumagai ,&nbsp;Chika Matsumoto ,&nbsp;Noriaki Takeguchi","doi":"10.1016/0922-4106(95)90137-X","DOIUrl":"10.1016/0922-4106(95)90137-X","url":null,"abstract":"<div><p>Gastric enterochromaffin-like (ECL) cells were isolated from rat gastric fundic mucosa by Percoll density-gradient centrifugation and counter-flow elutriation. About 67% of cells in the purified cell suspension were ECL cells, which were reacted with anti-histidine decarboxylase antibody. A23187, a calcium ionophore, at 0.1-10 μM induced histamine release from the ECL cell-rich suspension, indicating that the Ca²⁺ pathway is involved in the mechanism of histamine release from ECL cells. A23187 at 5 μM significantly increased outward-rectifier cationic current in 62% of cells in the ECL cell-rich fraction. A23187-sensitive cells showed acridine orange uptake. In single-channel recordings, a Ca²⁺-dependent outward-rectifier K⁺ channel of large conductance (146 ± 22 picosiemens) was found in the cell that showed acridine orange uptake. The channel opened in a voltage-dependent manner at 0.1 μM of intracellular free Ca²⁺ concentration. These results may suggest that opening of the Ca²⁺-activated K⁺ channel is one of the steps involved in the mechanism of histamine release in ECL cells.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 153-158"},"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)90137-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19545915","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}