Edema‐induced alterations in the regulation of myosin light chain phosphorylation in intestinal smooth muscle.

Abstract

We have shown that edema decreases intestinal contractile activity via decreased intestinal smooth muscle myosin light chain (MLC) phosphorylation. The objective of this study was to determine the mechanism by which edema decreases MLC phosphorylation. Thus, regulation of MLC phosphorylation was studied in a rodent model of intestinal edema. Edema was induced by a combination of resuscitative fluid administration and induction of mesenteric venous hypertension. Edema‐induced changes in MLC kinase (MLCK) activity and phosphorylation of MYPT1 subunit of MLC phosphatase (MLCP) were measured in intestinal smooth muscle. Phosphorylation of the MYPT1 subunit in the presence of rho kinase (ROK), zipper interacting protein kinase (ZIPK), and p21 activated kinase (PAK) inhibitors, Y‐27632, SM‐1 peptide, and IPA‐3 respectively, was also measured. No significant changes in MLCK activity were observed in the edematous intestinal smooth muscle. In contrast, phosphorylation of the MYPT1 subunit of MLCP was significantly decreased in edematous intestinal smooth muscle compared to controls. Data suggest that both ROK and ZIPK were involved in edema‐induced decreases in MYPT1 phosphorylation. We conclude from these data that edema‐induced decreases in the inhibitory phosphorylation of MYPT1 subunit of MLCP via regulation of ROK and ZIPK result in decreased MLC phosphorylation in edematous intestinal smooth muscle.