Myosin light chain phosphorylation and Mn2+ -dependent norepinephrine-induced contractions in guinea-pig vas deferens.
We have reported that norepinephrine but not K+ induced a sustained and dose-dependent contraction without extracellular Ca2+ and Mn2+ in Ca2+-depleted Mn2+-loaded vas deferens from the guinea-pig. In the present study, we determined the phosphorylation of the 20-kDa myosin light chain and examined the effects of inhibitors of calmodulin and myosin light chain kinase on the Mn2+-dependent norepinephrine-induced contraction in order to evaluate the contribution of phosphorylation to this contraction. W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-homopiperazine] and wortmannin inhibited this contraction. However, the Mn2+-dependent norepinephrine-induced contraction developed without a significant increase in the phosphorylation of the 20-kDa myosin light chain. In beta-escin-permeabilized preparations, Mn2+ induced contractions that were inhibited by ML-9. These results suggest that the activation of myosin light chain kinase is essential for the development of Mn2+-dependent norepinephrine-induced contractions and that the phosphorylation of myosin light chain may act as a trigger for these contractions.
Tsunobuchi-Ushijima
H
H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Okuno
H
H
Gomi
Y
Y
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009119:Muscle Contraction; D018994:Myosin Light Chains / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine; D010766:Phosphorylation; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology*
D001381:Azepines; D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; C056218:ML 9; D008345:Manganese; D009219:Myosin-Light-Chain Kinase; D002118:Calcium; D009638:Norepinephrine