Effect of aging on some dru-receptor mechanisms

In isolated rat vas deferens, the potency of α_1 -adrenoceptor stimulant increased with age from 3 to 18 weeks, but decreased thereafter with age from 18 to 60 weeks. Similar results were obtained in isolated rat aorta and rabbit iris dilator. The potencies of isoprenaline, which were estimated in tracheas from 3- to 100-week-old guinea pigs, increased with age in the presence of cortison, an extraneuronal uptake inhibitor, but decreased in the absence of it, suggesting that extraneuronal uptake plays an important role in the β-adrenergic action in older animals. An age-related increase in the potency of isoprenaline in the tracheas treated with cortisone was observed. The results obtained suggest that changes in α_1 - and β -adrenoceptor mechanisms are due to changes in their receptor densities, but not to changes in affinities of the agonists to their receptors. It was, furthermore, observed that the decrease in potency of isoprenaline in the tracheas from 100-week-old guinea pigs is due to a change in the post β -receptor processes in responsiveness. On the other hand, potencies of competitive antagonists did not alter with aging. No age-related changes were observed in muscarine, nicotine and serotonin receptor mechanisms. Effects of aging on inhibitory potency of diltiazem, a Ca ions channel blocker, were tested. An inverse relationship between potency of diltiazem and receptor density of agonist (e.g. norepinephrine) used was found. However, no age-related change in potency of diltiazem was observed, when agonist (e.g. acetylcholine), whose potency does not alter with age, was used. Effects of aging on nerve activity were also tested. Twitch response of and amount of acetylcholine released from rabbit iris sphincter, which is innervated by the cholinergic nerve, induced by field stimulation altered with age. However, no observations mentioned above were obtained in rabbit iris dilator, which is innervated by the adrenergic nerve. The present results indicate that the age of animals should be noted to estimate the potency of a new drug. Effects of aging on M_1 - and M_3 -muscarinic potencies of 1-methyl-5-chloroindoline methobromide, a cholino- mimetic drug (Takayanagi, I. et al. Japan. J. Pharmacol.21,31 1-316, 1971), will be reported as an example.