INHIBITION OF POLYAMINE SYNTHESIS INFLUENCES CONTRACTILITY OF INTESTINAL SMOOTH-MUSCLE IN CULTURE

Smooth muscle strips from guinea pig ileum were cultured for 5 days an d then tested for contractile properties to investigate whether endoge nous polyamines influence excitation-contraction coupling. Inhibition of spermidine and spermine synthesis by culture in the presence of the adenosylmethionine decarboxylase (EC4.1.1.50) inhibitor CGP-48664 (1- 10 mu M) decreased spermidine and spermine levels by 50% and increased putrescine by 20-fold. After culture with 10 mu M, but not 1 mu M, CG P-48664, the relationship between extracellular Ca2+ concentration and force in high K+-depolarized strips was shifted to the right, and pha sic contractile activity as well as sensitivity to muscarinic stimulat ion was enhanced. When spermidine and spermine (each 50 mu M) were ava ilable for cellular uptake during culture in the presence of 10 mu M C GP-48664, spermidine and spermine concentrations were increased, and t he effect on Ca2+ sensitivity was reversed. In strips cultured with 0 or 1 mu M CGP-48664 in the presence of 50 mu M spermidine and 50 mu M spermine, no effect on Ca2+ sensitivity was observed. Force developmen t relative to intracellular Ca2+ concentration was decreased in CGP-48 664 (10 mu M)-treated strips. The results suggest that endogenous poly amines influence excitation-contraction coupling in smooth muscle, alt hough overall tissue concentrations may not reflect the polyamine pool s responsible for this effect.