title: Adenosine 3', 5'-monophosphorothioate (Rp-isomer) induces down-regulation of surface cyclic AMP receptors without receptor activation in Dictyostelium discoideum.
abstract: cAMP induces the activation and subsequent desensitization of adenylate cyclase in Dictyostelium discoideum. cAMP also induces down-regulation of surface cAMP receptors. Desensitization of adenylate cyclase is composed of a rapidly reversible component (adaptation) and a slowly reversible component related to down-regulation of surface cAMP receptors (Van Haastert, P.J.M. (1987) J. Biol. Chem. 262, 7700-7704). The agonistic and antagonistic activities of the cAMP derivative adenosine 3',5'-monophosphorothioate ((Rp)-cAMPS) for these responses were investigated. (Rp)-cAMPS competes with cAMP for binding to different receptor forms with an apparent Ki = 5 microM. (Rp)-cAMPS does not activate adenylate cyclase and antagonizes the cAMP-induced activation with an apparent Ki = 5 microM. (Rp)-cAMPS induces down-regulation of surface cAMP receptors with EC50 = 5 microM. (Rp)-cAMPS induces desensitization of adenylate cyclase, which is not rapidly reversible. These results indicate that desensitization of adenylate cyclase by (Rp)-cAMPS is due to down-regulation of surface cAMP receptors and not to adaptation. We conclude that down-regulation of surface cAMP receptors does not require their activation or modification involved in adaptation.
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation; D007700:Kinetics; D011953:Receptors, Cyclic AMP / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology*
chemical_list: D011953:Receptors, Cyclic AMP; D013873:Thionucleotides; C014308:adenosine 5'-phosphorothioate; D000249:Adenosine Monophosphate; D000262:Adenylyl Cyclases; D004229:Dithiothreitol