Effect of lithium on smooth muscle contraction and phosphorylation of myosin light chain by MLCK

Abstract

The aims of our study were to investigate into the effect of lithium on smooth muscle contraction and phosphorylation of myosin light chain (MLC20) by MLCK and to find out the clue of its mechanism. Isolated rabbit duodenum smooth muscle strips were used to study the effects of lithium on their contractile activity under the condition of Krebs’ solution by means of HW400S constant temperature smooth muscle trough. Myosin and MLCK were purified from the chicken gizzard smooth muscle. Myosin phosphorylation was determined by Glycerol-PAGE, myosin Mg2+-ATPase activity was measured by Pi liberation method. Lithium (10-40 mM) inhibited the contraction in duodenum in a dose-related and time-dependent manner. Lithium could also inhibit the extent of myosin phosphorylation in a dose-related and time-dependent manner, whereas it inhibited Mg2+-ATPase activity in a dose-related manner. Lithium inhibited smooth muscle contraction by inhibition of myosin phosphorylation and Mg2+-ATPase activity.

Transcriptome and Proteome Profiling of Primary Human Gastric Interstitial Cells of Cajal Predicts Pacemaker Networks

“… 16 Further investigations of this predicted network will help determine their functional relevance in ICC-mediated regulation gastric smooth muscle contraction. For example, the effect of activators or inhibitors on these candidate proteins, such as incadronate for CAV1 54 and lithium for MYLK, 55 to explore their impact on pacemaker activity using electrophysiology and/or calcium imaging on cultured KIT low /CD45 – /CD11B – ICC, as has been similarly conducted using carbachol in cultured mouse ICC from the small intestine. 56 Such studies could have major clinical implications in identifying candidate small molecules capable of altering ICC electrophysiology, which in turn may lead to clinical trials investigating the potential for small molecules to improve pacemaker activity in patients with functional GI motility disorders where ICC networks are altered (eg, gastroparesis).…”