B. J. Davis, M. Wiener, C. R. Chapple, D. J. Sellers, R. Chess-Williams
{"title":"人输精管α 1l -肾上腺素能受体亚型的功能和放射配体结合特性","authors":"B. J. Davis, M. Wiener, C. R. Chapple, D. J. Sellers, R. Chess-Williams","doi":"10.1111/aap.12023","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>\n \n </p><ol>\n \n \n <li>Alpha<sub>1</sub>-adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α<sub>1A</sub>-adrenoceptors, and this study investigated whether the low affinity state of this receptor (α<sub>1L</sub>-adrenoceptor) is involved in mediating contractions of this tissue.</li>\n \n \n <li>The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [<sup>3</sup>H]tamsulosin binding experiments to identify the α<sub>1</sub>-adrenoceptor subtype population present in the human vas deferens.</li>\n \n \n <li>The α<sub>1A</sub>-adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pK<sub>d</sub> = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α<sub>1D</sub>-adrenoceptor selective) gave a low affinity estimate (pK<sub>d</sub> = 6.7), whilst tamsulosin (α<sub>1A</sub>- and α<sub>1D</sub>-adrenoceptor selective) had a high affinity (pK<sub>d</sub> = 9.9).</li>\n \n \n <li>[<sup>3</sup>H]Tamsulosin bound to human vas deferens membranes with a high affinity (pK<sub>d</sub> = 10.0). Prazosin, RS17053 and BMY7378 competed with [<sup>3</sup>H]tamsulosin with low affinities for a single population of binding sites (pK<sub>d</sub> values of 8.5, 7.2 and 6.3, respectively).</li>\n \n \n <li>These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α<sub>1</sub>-adrenoceptors which have the pharmacological properties of the putative α<sub>1L</sub>-adrenoceptor, the same functional receptor previously identified in the human prostate.</li>\n </ol>\n \n </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":"34 3-4","pages":"41-49"},"PeriodicalIF":0.0000,"publicationDate":"2015-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12023","citationCount":"5","resultStr":"{\"title\":\"Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens\",\"authors\":\"B. J. Davis, M. Wiener, C. R. Chapple, D. J. Sellers, R. Chess-Williams\",\"doi\":\"10.1111/aap.12023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>\\n \\n </p><ol>\\n \\n \\n <li>Alpha<sub>1</sub>-adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α<sub>1A</sub>-adrenoceptors, and this study investigated whether the low affinity state of this receptor (α<sub>1L</sub>-adrenoceptor) is involved in mediating contractions of this tissue.</li>\\n \\n \\n <li>The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [<sup>3</sup>H]tamsulosin binding experiments to identify the α<sub>1</sub>-adrenoceptor subtype population present in the human vas deferens.</li>\\n \\n \\n <li>The α<sub>1A</sub>-adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pK<sub>d</sub> = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α<sub>1D</sub>-adrenoceptor selective) gave a low affinity estimate (pK<sub>d</sub> = 6.7), whilst tamsulosin (α<sub>1A</sub>- and α<sub>1D</sub>-adrenoceptor selective) had a high affinity (pK<sub>d</sub> = 9.9).</li>\\n \\n \\n <li>[<sup>3</sup>H]Tamsulosin bound to human vas deferens membranes with a high affinity (pK<sub>d</sub> = 10.0). Prazosin, RS17053 and BMY7378 competed with [<sup>3</sup>H]tamsulosin with low affinities for a single population of binding sites (pK<sub>d</sub> values of 8.5, 7.2 and 6.3, respectively).</li>\\n \\n \\n <li>These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α<sub>1</sub>-adrenoceptors which have the pharmacological properties of the putative α<sub>1L</sub>-adrenoceptor, the same functional receptor previously identified in the human prostate.</li>\\n </ol>\\n \\n </div>\",\"PeriodicalId\":100151,\"journal\":{\"name\":\"Autonomic and Autacoid Pharmacology\",\"volume\":\"34 3-4\",\"pages\":\"41-49\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2015-03-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1111/aap.12023\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autonomic and Autacoid Pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/aap.12023\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/aap.12023","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens
Alpha1-adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A-adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L-adrenoceptor) is involved in mediating contractions of this tissue.
The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [3H]tamsulosin binding experiments to identify the α1-adrenoceptor subtype population present in the human vas deferens.
The α1A-adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D-adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A- and α1D-adrenoceptor selective) had a high affinity (pKd = 9.9).
[3H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [3H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively).
These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1-adrenoceptors which have the pharmacological properties of the putative α1L-adrenoceptor, the same functional receptor previously identified in the human prostate.