title: Upregulation of adrenergic beta receptor subtypes in the senescent rat heart.
abstract: Beta receptors in older hearts respond to procedures which cause upregulation (N. Tumer et al., J. Gerontol., 1989, in press). To determine whether a particular beta receptor subtype is responsible for the development of upregulation as a function of age, we studied the ratio of beta 1- to beta 2-adrenergic receptors in the membrane preparations from the ventricles of Fischer-344 hearts at 6 and 24 months of age. The animals were injected with 6-hydroxydopamine hydrobromide (6-OHDA) (2 x 50 mg/kg, i.v.) on days 1 and 8 and they were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. [125I]iodopindolol (IPIN) was used as the radioligand at the final concentration of 110 pM. Inhibition of specific IPIN binding was studied by adding ICI 89,406 (beta 1-selective antagonist) and ICI 118,551 (beta 2-selective antagonist) at 25 pM to 40 microM. The relative proportions of the beta receptor subtypes were determined using a competition radioligand selective binding and computer modeling technique. The ventricles contained about 67% beta 1 and 33% beta 2-adrenergic receptors in hearts isolated from 6- and 24-month old rats; the ratio remained the same in sympathectomized animals. These data suggest that both subtypes of cardiac adrenergic receptors participate in the response to chemical denervation by 6-OHDA regardless of age.
authors.affiliation: Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
authors.forename: N
authors.initials: N
authors.lastname: Tumer
authors.forename: W T
authors.initials: WT
authors.lastname: Houck
authors.forename: J
authors.initials: J
authors.lastname: Roberts
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006892:Hydroxydopamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine