title: Effects of age on alpha 1-adrenoceptor subtypes in the heart ventricular muscle of the rat.
abstract: The effects of ageing on alpha 1-adrenoceptor subtypes have been examined in heart ventricular muscle of young (2-3 months) and middle-aged (18 months) Sprague-Dawley rats. Radioligand binding studies with [3H]prazosin revealed an age-related loss of binding sites (Bmax 56.7 +/- 1.93 fmol (mg protein)-1 age 2 months vs 31.7 +/- 2.45 fmol (mg protein)-1 age 18 months) not followed by changes in the dissociation constant value (Kd 0.16 +/- 0.03 nM age 2 months and 0.10 +/- 0.03 nM age 18 months). Competition curves with WB 4101 showed two distinct sites with different affinities, the proportion of sites with high affinity being similar for both age groups (22.2 +/- 1.89% vs 17.8 +/- 1.96% for animals aged 2 and 18 months, respectively). Agonist displacement curves of [3H]prazosin indicate the existence of two different affinity sites for the agonist, that are maintained regardless of the ageing process (R(high) = 16.2 +/- 1.54% and R(low) = 83.8 +/- 1.89% in rats aged 2 months and R(high) = 16.3 +/- 3.23% and R(low) = 83.7 +/- 3.95% in rats aged 18 months). The fractional inactivation of alpha 1-adrenoceptors by chloroethylclonidine resulted in a loss of [3H]prazosin specific binding, and a percentage of 22.5 +/- 0.95 and 22.6 +/- 4.2 of remaining binding sites for the groups of 2 and 18 months of age, respectively. The percentage of chloroethylclonidine-insensitive [3H]prazosin binding sites was similar to those with high affinity for WB4101. The present study confirms a decline of alpha 1-adrenoceptors with increasing age and reveals that the equilibrium of the expression of the two existing subpopulations of the receptor is maintained during ageing.
authors.affiliation: Departament de Farmacologia i Psiquiatria, Universitat Autònoma de Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Gascón
authors.forename: M
authors.initials: M
authors.lastname: Dierssen
authors.forename: F
authors.initials: F
authors.lastname: Màrmol
authors.forename: N M
authors.initials: NM
authors.lastname: Vivas
authors.forename: A
authors.initials: A
authors.lastname: Badia
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics; D000375:Aging / Q000378:metabolism*; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000477:Alkylating Agents; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin