Mechanisms of Spermine‐ and N1‐Acetylspermine‐induced Relaxation on Rat Uterine Smooth Muscle In‐vitro

Abstract

The effect of the natural polyamines, spermine and N1-acetylspermine, on rat uterine smooth muscle and cAMP phosphodiesterase activity has been studied to determine the actions that contribute to their inhibitory effect on smooth muscle. Both drugs produce concentration-dependent relaxation of KCl-induced tonic contraction in rat uterus, which could be counteracted by CaCl2 (0·1–3·0 mM). 1(5 Isoquinolinyl-sulphonyl)-2-methyl-piperazine (1 μM) and N-p-tosyl-l-phenylalanine-chloromethyl-ketone (3 μm), inhibitors of protein kinase C and A, respectively, did not modify the relaxant effect of spermine or N1-acetylspermine. Basal activity and calmodulin-stimulated activity of cAMP phosphodiesterase was inhibited in a concentration-dependent way by spermine, but not by N1-acetylspermine. These results suggest that spermine and N1-acetylspermine produce their spasmolytic effect on rat uterus through a calcium-antagonistic action. The inhibition of phosphodiesterase and calmodulin does not appear to be involved in the relaxant effect induced by spermine, as it occurs at different concentrations and is unmodified by the protein kinase A inhibitor.