EFFECTS OF NONSPECIFIC SMOOTH MUSCLE RELAXANTS ON CALCIUM-UPTAKE BY MICROSOMAL FRACTION AND THEIR INHIBITORY ACTION IN RABBIT TAENIA COLI

Abstract

Effects of nonspecific smooth muscle relaxants, papaverine and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride) on Ca-uptake by a microsomal fraction and mechanical activity in the rabbit taenia coli were studied. Papaverine which inhibits cyclic AMP phosphodiesterase increased Ca-uptake by the microsomal fraction in a concentration of 10^-5 M but not in a concentration of 10^-4 M. Potentiation of Ca-uptake by papaverine is considered to be due to the increase of cyclic AMP as the results of the inhibition of phosphodiesterase. Aspaminol which is found to have little inhibitory action on phosphodiesterase activity inhibited Ca-uptake by the microsomal fraction. This inhibition by Aspaminol was abolished by the increase of Ca-concentration in the reaction medium. Noncompetitive antihistaminic activity of Aspaminol was considerably reduced by an increase of external Ca-concentration, while the increase of external Ca-concentration slightly decreased antihistaminic activity of papaverine. Furthermore, contraction of KCl-depolarizd taenia coli induced by CaCl₂ was inhibited competitively by Aspaminol and noncompetitively by papaverine. These results suggest that Aspaminol competes with Ca ions at a surface site of muscle membrane concerned with Ca-uptake process, thus decreasing the supply of Ca ions to the contractile elements and that papaverine may have inhibitory actions on Ca-uptake by the microsomal fraction in addition to stimulatory action which seems to be mediated through cyclic AMP. These actions on Ca-uptake may induce smooth muscle relaxation.