title: The effect of inhibitors of receptor internalization on the desensitization and resensitization of three Gs-coupled receptor responses.
abstract: Many G protein-coupled receptors (GPCRs) are known to internalize following agonist exposure, however the relative importance of this mechanism for the desensitization and resensitization of different GPCRs is unclear. In the present study, we have pretreated NG108-15 cells with hypertonic sucrose or concanavalin A (con A), to investigate the effects of these inhibitors of internalization on the agonist-induced desensitization and subsequent resensitization of three Gs-coupled receptor responses. Incubation of cells with sucrose or con A did not affect subsequent acute agonist stimulation of the A2A adenosine receptor or the agonist-induced desensitization of this receptor response. However, the resensitization of the A2A adenosine receptor response following agonist removal was abolished in the presence of sucrose or con A. Sucrose or con A treatment affected neither the desensitization nor resensitization of IP-prostanoid receptor responsiveness. On the other hand con A but not sucrose reduced the agonist-induced desensitization of secretin receptor responsiveness. However, secretin receptor responsiveness did not resensitize within the time period studied whether or not inhibitors of internalization were present. These results indicate that receptor internalization appears to subserve different functions for different GPCRs.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of Bristol.
authors.forename: S J
authors.initials: SJ
authors.lastname: Mundell
authors.forename: E
authors.initials: E
authors.lastname: Kelly
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006822:Hybrid Cells; D051379:Mice; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D043705:Receptor, Adenosine A2A; D044006:Receptors, Epoprostenol; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051552:beta-Adrenergic Receptor Kinases
chemical_list: D010627:Phenethylamines; C491910:Ptgir protein, mouse; C491909:Ptgir protein, rat; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D044006:Receptors, Epoprostenol; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D011982:Receptors, Prostaglandin; D018047:Receptors, Purinergic P1; C029937:secretin receptor; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D000241:Adenosine