Inhibition of polyamine synthesis influences contractility of intestinal smooth muscle in culture.
Smooth muscle strips from guinea pig ileum were cultured for 5 days and then tested for contractile properties to investigate whether endogenous 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 microM) decreased spermidine and spermine levels by 50% and increased putrescine by 20-fold. After culture with 10 microM, but not 1 microM, CGP-48664, the relationship between extracellular Ca2+ concentration and force in high K(+)-depolarized strips was shifted to the right, and phasic contractile activity as well as sensitivity to muscarinic stimulation was enhanced. When spermidine and spermine (each 50 microM) were available for cellular uptake during culture in the presence of 10 microM CGP-48664, spermidine and spermine concentrations were increased, and the effect on Ca2+ sensitivity was reversed. In strips cultured with 0 or 1 microM CGP-48664 in the presence of 50 microM spermidine and 50 microM spermine, no effect on Ca2+ sensitivity was observed. Force development relative to intracellular Ca2+ concentration was decreased in CGP-48664 (10 microM)-treated strips. The results suggest that endogenous polyamines influence excitation-contraction coupling in smooth muscle, although overall tissue concentrations may not reflect the polyamine pools responsible for this effect.
Swärd
K
K
Department of Physiology and Neuroscience, University of Lund, Sweden.
Nilsson
B O
BO
Hellstrand
P
P
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007189:Indans / Q000494:pharmacology*; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011073:Polyamines / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D000578:Amidines; D004791:Enzyme Inhibitors; D007189:Indans; D011073:Polyamines; C082408:4-amidinoindan-1-one 2'-amidinohydrazone; D013096:Spermine; D012437:Adenosylmethionine Decarboxylase; D011188:Potassium; D002118:Calcium; D013095:Spermidine; D011700:Putrescine