[Effects of aging on drug receptor mechanisms in smooth muscles].
The effects of aging on some drug receptor mechanisms were studied in isolated smooth muscles. Potencies of alpha- and beta-adrenoceptor agonists increased from the young stage to the adult stage and decreased slowly thereafter to the old stage. The affinities of the adrenergic drugs on their receptors did not alter with aging. Excellent relationships between the potencies or efficacies of the agonists and the amounts of receptors or receptor reserve were found, suggesting that changes in the adrenoceptor mechanisms with aging were due to changes in the amount of receptors. However, it was also found that the decrease in the potency of beta-adrenoceptor agonists in preparations from the older animals was due to the change in post beta-adrenoceptor processes in responsiveness. However, the serotonin, acetylcholine (ACh) and tachykinin (NK2) receptor mechanisms did not alter with aging. Enzyme activities altered with aging. For example, activities of acetylcholinesterase and choline acetyltransferase decreased with aging. The potencies of nicotine, which accelerates ACh release, and exogenously applied ACh were modified by the change in enzyme activities with aging. Similar observations were obtained in the tachykinin (NK2) receptor mechanism. Effects of aging on physiological functions seem to be complementary. In iris dilator muscles, the potency of norepinephrine (NE), which altered with aging, was proportional in the receptor reserve. No age-related change was observed in the activity of sympathetic nerves, which innervate the iris dilator muscles. On the other hand, in iris sphincter muscles innervated by parasympathetic nerves, the ACh (muscarine) receptor mechanisms did not alter, but the activity in cholinergic nerves changed with aging.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
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Takayanagi
D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D015288:Neurokinin A / Q000502:physiology; D011817:Rabbits; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011978:Receptors, Nicotinic; D015288:Neurokinin A; D000109:Acetylcholine