Age-related alteration of inhibitory effects of isradipine on alpha 1-adrenoceptor mediated responses

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
S KanaiM Satoh

Abstract

We studied age-related alteration of inhibitory effects of a Ca2+ channel antagonist, isradipine, on alpha 1-adrenoceptor mediated responses in 6-, 10-, and 40-week-old rats. Age-related changes were observed in the inhibitory effects of isradipine on the norepinephrine-induced maximum contractions in the isolated thoracic aorta, the amplitude of the Ca(2+)-evoked increase of intracellular Ca2+ concentration and sustained contraction in fura-2-loaded preparations and the maximum number of binding sites (Bmax) of [3H] (+)-isradipine to aortic membranes. The dissociation constant (KD) of [3H] (+)-isradipine did not alter with age. In anesthetized rats, isradipine inhibited the dose-response curves of norepinephrine on the blood pressure in 6- and 40-week-old animals more effectively than those in 10-week-old animals. An inverse relationship between the potency of norepinephrine in the isolated thoracic aorta, the inhibitory effects of isradipine on the norepinephrine-induced maximum contractions and the logarithm of Bmax obtained in the [3H] (+)-isradipine binding experiment were found. These results suggest that the age-related alteration of inhibitory effects of isradipine on alpha 1-adrenoceptor mediated contractile responses ...Continue Reading

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.