title: Differential regulation of human alpha1-adrenoceptor subtypes.
abstract: We have compared the agonist-induced down-regulation of human alpha1A-, alpha1B- and alpha1D-adrenoceptors upon stable expression in rat-1 fibroblasts. During a 24-h incubation the agonist phenylephrine downregulated alpha1A- and alpha1 -adrenoceptors in a concentration-dependent manner. While maximum downregulation was similar for both subtypes, the threshold concentration for significant reductions was markedly higher for alpha1A- than for alpha(1B-adrenoceptors (10 microM vs. 100 nM). The downregulation of both subtypes by 100 microM phenylephrine was time-dependent, and significant reductions were observed already after 2-4 h. In contrast, incubation of alpha1D-adrenoceptor-expressing cells with phenylephrine increased receptor number in a time- and concentration-dependent manner. The downregulation of alpha1B-adrenoceptors by 100 microM phenylephrine for 24 h was accompanied by a matching reduction in mRNA abundance, but no such reduction was seen for alpha-adrenoceptors. These treatment conditions also caused a functional desensitization of agonist-stimulated inositol phosphate formation for alpha1A- and alpha1B- but not for alpha1D-adrenoceptors. Treatment with the phorbol ester phorbol-12-myristate-13-acetate did not change receptor density or mRNA abundance and did not cause functional desensitization. We conclude that human alpha1-adrenoceptor subtypes are differentially regulated by agonist treatment even if they are expressed in the same cell line.
authors.affiliation: Department of Medicine, University of Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Ruan
authors.forename: M
authors.initials: M
authors.lastname: Voller
authors.forename: J
authors.initials: J
authors.lastname: Schalken
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005347:Fibroblasts; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D013755:Tetradecanoylphorbol Acetate; D011224:Prazosin