Effect of aging on the response of guinea pig trachea to isoprenaline.
To study the effect of aging on the beta-adrenergic receptor potency of isoprenaline, tracheas from 3-, 6-, 10-, 40- and 100-week-old guinea pigs were used as test tissues. The pD2 values (potency) of isoprenaline increased with age in tracheas treated with corticosterone, but decreased in untreated tracheas. The pA2 value of propranolol against isoprenaline estimated in the treated tracheas did not change with age. Specific binding of [3H]-dihydroalprenolol to the microsomal fractions from the tracheal muscles from 6-, 10- and 40-week-old guinea pigs was analyzed with Scatchard plots. The capacity of maximum binding sites of [3H]-dihydroalprenolol increased with increasing age, while its dissociation constant did not change. Age-related increase in the potency of isoprenaline in the tracheas treated with corticosterone is considered to be due to the increase in the total amount (density) of beta-adrenoceptors. However, the potency of the drug in untreated tracheas decreased with age. These results suggest that extraneuronal uptake plays an important role in the beta-adrenergic action of isoprenaline in older (40 and 100 weeks) guinea pigs.
Takayanagi
I
I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Kawano
K
K
Koike
K
K
D000375:Aging / Q000502:physiology*; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D004082:Dihydroalprenolol; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D011433:Propranolol; D007545:Isoproterenol; D003345:Corticosterone