The inhibitory effect of Li+ on contractile elements of intestinal smooth muscle.
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 microM) and histamine (1 microM) 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 microM 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 ATP gamma S and 3 microM 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.
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000032:analysis / Q000493:pharmacokinetics; D004910:Erythrocyte Membrane / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism
D008094:Lithium; D009219:Myosin-Light-Chain Kinase; D010744:Phosphoric Monoester Hydrolases; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium