{"id":115490,"date":"2014-04-04T00:00:00","date_gmt":"2014-04-04T00:00:00","guid":{"rendered":""},"modified":"2014-04-04T00:00:00","modified_gmt":"2014-04-04T00:00:00","slug":"compartimentacion-celular-y-acoplamiento-funcional-a-protea%c2%adnas-g-heterotrimericas-del-receptor-cannabinoide-cb1-en-corteza-cerebral-de-mama%c2%adferos-rata-y-humano-regulacion-en-un-modelo-an","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/farmacologia-molecular\/compartimentacion-celular-y-acoplamiento-funcional-a-protea%c2%adnas-g-heterotrimericas-del-receptor-cannabinoide-cb1-en-corteza-cerebral-de-mama%c2%adferos-rata-y-humano-regulacion-en-un-modelo-an\/","title":{"rendered":"Compartimentaci\u00f3n celular y acoplamiento funcional a prote\u00ednas g heterotrim\u00e9ricas del receptor cannabinoide cb1 en corteza cerebral de mam\u00edferos (rata y humano). regulaci\u00f3n en un modelo animal de desa"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Leyre Echeazarra Escudero <\/strong><\/h2>\n<p>En la presente tesis doctoral se ha estudiado la compartimentaci\u00f3n celular y el acoplamiento funcional a prote\u00ednas g heterotrim\u00e9ricas del receptor cannabinoide cb1 en la corteza cerebral de mam\u00edferos (rata y humano) mediante t\u00e9cnicas de inmunodetecci\u00f3n con anticuerpos espec\u00edficos (inmunofluorescencia, inmunohistoquimia y western blot) y t\u00e9cnicas de fijaci\u00f3n de radioligandos y de estimulaci\u00f3n de la fijaci\u00f3n del nucle\u00f3tido [35s]gtp\u00c2\u00bfs. Nuestros resultados demuestran la localizaci\u00f3n del receptor cb1 en balsas lip\u00eddicas (lipid rafts) y la presencia mayoritaria de las isoformas \u00c2\u00bfo y \u00c2\u00bfi3 de la familia de prote\u00ednas g\u00c2\u00bfi\/o. Asimismo, demostramos c\u00f3mo la alteraci\u00f3n del colesterol impacta en la capacidad de acoplamiento del receptor a las prote\u00ednas g\u00c2\u00bfi\/o, resultando en un aumento en la eficacia de la respuesta (emax). Por otro lado, a pesar de las evidencias presentadas en esta tesis doctoral, tanto farmacol\u00f3gicas como bioqu\u00edmicas, que sugieren la expresi\u00f3n del receptor cb1 en el n\u00facleo celular, la  funcionalidad observada en las preparaciones enriquecidas en elementos nucleares no  puede atribuirse ni a una expresi\u00f3n funcional de receptores cb1 en n\u00facleos neuronales ni en mitocondrias. Concluimos, por tanto, que el anticuerpo utilizado (cb1-go-cb1-af450-1, frontier science) parece reconocer de forma espec\u00edfica tanto el receptor cb1 como una prote\u00edna adicional de localizaci\u00f3n nuclear. Por \u00faltimo, dado el gran n\u00famero de evidencias, tanto anat\u00f3micas como farmacol\u00f3gicas, que relacionan al receptor cb1 con la respuesta al estr\u00e9s y el control de la homeostasis emocional, se ha estudiado la expresi\u00f3n y funcionalidad del receptor en secciones tisulares y en preparaciones de membrana obtenidas a partir de corteza cerebral y \u00e1reas l\u00edmbicas relacionadas en la rata zucker obesa, utilizada como modelo animal de desadaptaci\u00f3n cr\u00f3nica al estr\u00e9s. Nuestros resultados demuestran un aumento de la expresi\u00f3n y funcionalidad del receptor cb1 con respecto al fenotipo delgado, que se expresa de forma regi\u00f3n-selectiva en la corteza prefrontal medial, no habiendo diferencias ni en el hipocampo ni en la am\u00edgdala. De forma paralela, el estudio de la influencia del ritmo circadiano demuestra un aumento en el nivel de expresi\u00f3n del receptor cb1 presente en la am\u00edgdala \u00fanicamente en ratas zucker de fenotipo delgado sacrificadas en el momento de m\u00e1xima secreci\u00f3n de glucocorticoides (tarde).<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Compartimentaci\u00f3n celular y acoplamiento funcional a prote\u00ednas g heterotrim\u00e9ricas del receptor cannabinoide cb1 en corteza cerebral de mam\u00edferos (rata y humano). regulaci\u00f3n en un modelo animal de desa<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Compartimentaci\u00f3n celular y acoplamiento funcional a prote\u00ednas g heterotrim\u00e9ricas del receptor cannabinoide cb1 en corteza cerebral de mam\u00edferos (rata y humano). regulaci\u00f3n en un modelo animal de desa <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Leyre Echeazarra Escudero <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pa\u00eds vasco\/euskal herriko unibertsitatea<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 04\/04\/2014<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Joan Salles Alvira<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: pedro rolando Grandes moreno <\/li>\n<li>Jos\u00e9 Luis Lanciego perez (vocal)<\/li>\n<li>Rafael Franco fernandez (vocal)<\/li>\n<li>\u00c1lvaro D\u00edaz mart\u00ednez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Leyre Echeazarra Escudero En la presente tesis doctoral se ha estudiado la compartimentaci\u00f3n celular y el acoplamiento [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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