title: Enhanced cAMP response of naturally occurring mutant of human beta3-adrenergic receptor.
abstract: We have examined the functional significance of the naturally occurring mutation at position 64 of human beta3-adrenergic receptor (beta3AR), which changes the amino acid from tryptophan to arginine (W64R-beta3AR). The affinities of betaAR agonists for W64R-beta3AR expressed in COS-7 cells were not significantly different from those for wild type beta3AR. When two receptors are expressed at various expression levels, and stimulated with CGP12177A, they showed essentially the same EC50 values and maximal responses. Overexpression of Gi and Go, or the treatment with pertussis toxin did not affect the agonist-induced cAMP response, suggesting that Gi and Go did not contribute to the beta3AR-induced cAMP response. However, the enhanced cAMP response was observed when W64R-beta3AR was coexpressed with the adenylyl cyclase type III isoform, and stimulated by CGP12177A and isoproterenol. These results indicate that the cAMP response of W64R-beta3AR can be enhanced under the particular condition that adenylyl cyclase type III was coexpressed.
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Isogaya
authors.forename: Taku
authors.initials: T
authors.lastname: Nagao
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurose
mesh_terms: D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D037342:Pertussis Toxin; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D022702:Receptors, Adrenergic, beta-3 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; C033394:CGP 12177