Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade
Autor(a) principal: | |
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Data de Publicação: | 1999 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1038/sj.bjp.0702735 http://hdl.handle.net/11449/17473 |
Resumo: | 1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values. |
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Repositório Institucional da UNESP |
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Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockadeindoraminalpha(1)-adrenoceptorsvas deferensaorta1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values.UNESP, Inst Biociencias, Dept Pharmacol, BR-18600000 Botucatu, SP, BrazilUNIFESP, Escola Paulista Med, Dept Pharmacol, BR-0403406 São Paulo, BrazilUNESP, Inst Biociencias, Dept Pharmacol, BR-18600000 Botucatu, SP, BrazilStockton PressUniversidade Estadual Paulista (Unesp)Universidade Federal de São Paulo (UNIFESP)Pupo, A. S.Cavenaghi, DLCCampos, M.Morais, P. D.Jurkiewicz, N. H.Jurkiewicz, A.2014-05-20T13:49:03Z2014-05-20T13:49:03Z1999-08-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1832-1836application/pdfhttp://dx.doi.org/10.1038/sj.bjp.0702735British Journal of Pharmacology. Basingstoke: Stockton Press, v. 127, n. 8, p. 1832-1836, 1999.0007-1188http://hdl.handle.net/11449/1747310.1038/sj.bjp.0702735WOS:000082312500010WOS000082312500010.pdf2224433126054725Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBritish Journal of Pharmacology6.8102,603info:eu-repo/semantics/openAccess2023-11-26T06:17:10Zoai:repositorio.unesp.br:11449/17473Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:49:20.398990Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade |
title |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade |
spellingShingle |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade Pupo, A. S. indoramin alpha(1)-adrenoceptors vas deferens aorta |
title_short |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade |
title_full |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade |
title_fullStr |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade |
title_full_unstemmed |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade |
title_sort |
Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade |
author |
Pupo, A. S. |
author_facet |
Pupo, A. S. Cavenaghi, DLC Campos, M. Morais, P. D. Jurkiewicz, N. H. Jurkiewicz, A. |
author_role |
author |
author2 |
Cavenaghi, DLC Campos, M. Morais, P. D. Jurkiewicz, N. H. Jurkiewicz, A. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Pupo, A. S. Cavenaghi, DLC Campos, M. Morais, P. D. Jurkiewicz, N. H. Jurkiewicz, A. |
dc.subject.por.fl_str_mv |
indoramin alpha(1)-adrenoceptors vas deferens aorta |
topic |
indoramin alpha(1)-adrenoceptors vas deferens aorta |
description |
1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values. |
publishDate |
1999 |
dc.date.none.fl_str_mv |
1999-08-01 2014-05-20T13:49:03Z 2014-05-20T13:49:03Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/sj.bjp.0702735 British Journal of Pharmacology. Basingstoke: Stockton Press, v. 127, n. 8, p. 1832-1836, 1999. 0007-1188 http://hdl.handle.net/11449/17473 10.1038/sj.bjp.0702735 WOS:000082312500010 WOS000082312500010.pdf 2224433126054725 |
url |
http://dx.doi.org/10.1038/sj.bjp.0702735 http://hdl.handle.net/11449/17473 |
identifier_str_mv |
British Journal of Pharmacology. Basingstoke: Stockton Press, v. 127, n. 8, p. 1832-1836, 1999. 0007-1188 10.1038/sj.bjp.0702735 WOS:000082312500010 WOS000082312500010.pdf 2224433126054725 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
British Journal of Pharmacology 6.810 2,603 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1832-1836 application/pdf |
dc.publisher.none.fl_str_mv |
Stockton Press |
publisher.none.fl_str_mv |
Stockton Press |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128984480743424 |