title: Effect of age on vascular beta2-adrenergic receptor desensitization is not mediated by the receptor coupling to Galphai proteins.
abstract: Beta-adrenergic receptor (beta-AR)-mediated vasorelaxation declines with age. In the vasculature, beta2-AR undergoes protein kinase A-mediated desensitization that causes a switch in the G protein coupled to beta2-AR; Galphai links instead of Galphas. We exposed Fischer 344 rat aortae of increasing age to a desensitizing dose of isoproterenol, and determined its effect on beta2-AR-mediated vasorelaxation. Desensitization decreased beta2-AR-mediated vasorelaxation in young aortae only. Subsequently, we used pertussis toxin to block Galphai to determine whether changes in beta2-AR/G protein coupling occurred. Galphai inhibition did not reverse desensitization or the age-related change, but there appears to be a population of beta2-AR linked to Galphai, as pertussis toxin treatment improved beta2-AR-mediated vasorelaxation in aortae from animals of all ages. These findings suggest aortic beta2-AR in older animals may be maximally desensitized, which would explain impaired vasorelaxation. Our results also imply that protein kinase A-mediated beta2-AR desensitization may not be responsible for the age-related decline.
authors.affiliation: Portland VA Medical Center, Research Service, Portland, OR 97201, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Schutzer
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: John F
authors.initials: JF
authors.lastname: Reed
authors.forename: Scott L
authors.initials: SL
authors.lastname: Mader
mesh_terms: D000262:Adenylyl Cyclases / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases; D008790:Metoprolol; D007545:Isoproterenol