Effects of aging on alpha 2-adrenoceptor mechanisms in isolated guinea-pig tracheal preparations.
The effects of aging on alpha 2-adrenoceptor mechanisms in tracheal preparations isolated from 3-, 6-, 10-, 40- and 100-week-old guinea-pigs were studied. The potency of noradrenaline decreased with age. The specific binding of [3H]p-aminoclonidine to microsomal fractions prepared from tracheal smooth muscles from 6- and 40-week-old guinea-pigs was analysed by Scatchard analysis. The capacity of maximum binding sites of [3H]p-aminoclonidine was greater in the preparations from 40-week-old guinea-pigs than in 6-week-old animals, whereas the dissociation constant did not change with age. The amount of prostaglandin F2 alpha released by noradrenaline and the contractile response to prostaglandin F2 alpha decreased with age. These results suggest that an age-related decrease in the potency of noradrenaline is due to the decrease in the amount of excitable prostaglandin F2 alpha released by noradrenaline and in the contractile response to prostaglandin F2 alpha, but not to a change in the total number of alpha 2-adrenoceptors or in the dissociation constant of a drug from alpha 2-adrenoceptors. Extraneuronal uptake also plays a role in the response to noradrenaline in the tracheal preparations from older guinea-pigs.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
I
I
Takayanagi
K
K
Kawano
K
K
Koike
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; C016986:apraclonidine; D015237:Dinoprost; D003000:Clonidine; D015230:Prostaglandin D2; D003345:Corticosterone; D009638:Norepinephrine