The Inhibitory Effect of Li+ on Contractile Elements of Intestinal Smooth Muscle

[摘要] References(33)Cited-By(5)The mechanism of the inhibitory effect of Li+ on contraction was examined in guinea pig ileal longitudinal smooth muscle. Li+-substitution (68.4 mM) reversed contractions induced by high K+ (45.4 mM), carbachol (1 μM) and histamine (1 μM) without changing the cytosolic Ca2+ level. Li+ also had no effect on the increase in 45Ca2+ uptake stimulated by high K+. High K+ transiently increased myosin light chain (MLC) phosphorylation, reaching a peak at 6-9 sec. Li+-substitution inhibited the high K+-induced MLC phosphorylation. In permeabilized ileal strips, contraction induced by 1 μM Ca2+ was inhibited by 10 mM Li+ The inhibitory effect was antagonized by increasing the concentration of Ca2+ or calmodulin. In the permeabilized muscle in which MLC was previously thiophosphorylated with 1 mM ATPγS and 3 μM Ca2+, ATP induced contraction in Ca2+ free buffer. Li+ added during this contraction did not show an inhibitory effect. In contrast, when 30 mM Li+ was added during the thiophosphorylation, the contraction induced by the subsequent addition of ATP was inhibited. Li+ (30 mM) changed neither the rate of relaxation induced by removing external Ca2+ in permeabilized muscle nor the rate of dephosphorylation of MLC induced by crude phosphatase extracted from the ileum. Li+ (15 mM), on the other hand, inhibited the rate of phosphorylation of MLC caused by crude MLC kinase extracted from the ileum. Li+ did not inhibit the calmodulin activity as measured with the (Ca2+ + Mg2+)-ATPase activity of the erythrocyte membrane. These results suggest that the inhibitory effect of Li+ on contractions is attributable to the inhibition of MLC kinase in guinea pig ileum.

[学科分类] 药理学

[关键词] Li+ (lithium ion);Smooth muscle (intestine);Contractile element;Myosin light chain kinase;Cytosolic Ca2+ level