title: Epidermal growth factor (EGF)-induced up-regulation and agonist- and antagonist-induced desensitization and internalization of A1 adenosine receptors in a pituitary-derived cell line.
abstract: This report concerns the study of homologous and heterologous regulation of cell surface A1 adenosine receptors (A1R) in a pituitary-derived cell line. This has been possible by the use of the recently developed anti-A1R antibodies in immunocytochemical assays. Functional desensitization and internalization of A1R in GH4 cells occurred after treatment with agonist but also with antagonist. Epidermal growth factor (EGF) treatment led to the up-regulation of cell surface A1R in GH4 cells. Confocal analysis evidenced an EGF-induced increase of A1R present in intracellular clathrin-coated vesicles. The up-regulation was blocked by actinomycin D thus suggesting the involvement of protein synthesis in the effect induced by the growth factor. These results constitute the first example of adenosine receptor regulation by EGF and one of the few examples of antagonist-induced desensitization and internalization among G-protein-coupled receptors.
authors.affiliation: Facultat de Quimica, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Martí i Franquès 1, 08028, Barcelona, Catalunya, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Navarro
authors.forename: R
authors.initials: R
authors.lastname: Zapata
authors.forename: E I
authors.initials: EI
authors.lastname: Canela
authors.forename: J
authors.initials: J
authors.lastname: Mallol
authors.forename: C
authors.initials: C
authors.lastname: Lluis
authors.forename: R
authors.initials: R
authors.lastname: Franco
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D010902:Pituitary Gland / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D011500:Protein Synthesis Inhibitors; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D003609:Dactinomycin; C047235:N-(1-methyl-2-phenylethyl)adenosine; D004815:Epidermal Growth Factor; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D002118:Calcium