title: Functional alpha 2-adrenergic receptor-Gs coupling undergoes agonist-promoted desensitization in a subtype-selective manner.
abstract: Recently it has become clear that alpha 2-adrenergic receptors (alpha 2AR) functionally couple to Gs as well as Gi, thus inducing a complex modulation of adenylyl cyclase activity. It is unknown whether alpha 2AR-Gs coupling undergoes agonist-promoted desensitization. Therefore, in CHO cells expressing the three cloned human alpha 2AR subtypes (alpha 2C10, alpha 2C4, and alpha 2C2), we assessed the ability of alpha 2AR-mediated stimulation of adenylyl cyclase activity to undergo short-term agonist-promoted desensitization. To isolate alpha 2AR-Gs coupling, cells were pretreated with pertussis toxin, which ablates Gi coupling. Following agonist exposure, both alpha 2C10- and alpha 2C2-mediated stimulation of adenylyl cyclase activity underwent marked desensitization. In distinct contrast, alpha 2C4-mediated stimulation of adenylyl cyclase activity underwent no agonist-promoted desensitization. Thus, alpha 2AR-Gs coupling undergoes agonist-promoted desensitization and does so in a subtype-selective manner.
authors.affiliation: Department of Medicine (Pulmonary), University of Cincinnati College of Medicine, OH 45267.
authors.forename: M G
authors.initials: MG
authors.lastname: Eason
authors.forename: S B
authors.initials: SB
authors.lastname: Liggett
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases