Calcium-independent activation of the contractile apparatus in smooth muscle of mouse aorta by protein phosphatase inhibition.

Autor: Knapp, Jörg, Aleth, Susanne, Balzer, Felix, Schmitz, Wilhelm, Neumann, Joachim
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Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology; Dec2002, Vol. 366 Issue 6, p562-569, 8p
Abstrakt: Smooth muscle contraction is primarily regulated by reversible phosphorylation of the 20-kDa light chains of myosin (MLC20) involving Ca2+-calmodulin-dependent myosin light chain kinase (MLCK) and serine/threonine protein phosphatases (PP). The aim of this study was to investigate the effects of the protein phosphatases (PP) type 1 (PP1) and type 2A (PP2A) inhibitor cantharidin (Cant), its structural analogue endothall (ETA) and microcystin LR (MC) on force of contraction and MLC20-phosphorylation in arterial smooth muscle of mouse aorta. Cant increased force of contraction and MLC20-phosphorylation in intact arterial rings of mouse aorta in the presence of Ca2+ whereas ETA and MC were ineffective under the same experimental conditions. In contrast, all compounds induced contraction and led to enhanced MLC20-phosphorylation in nominally Ca2+-free solution in fibers of mouse aorta permeabilised (skinned) with Triton X-100. In addition, Western blot analysis revealed that skinning of mouse aorta did not result in a loss of PP1 and PP2A compared to intact rings. Thus, both PP must be tightly bound to structural proteins, e.g. myosin. The findings indicate a Ca2+-independent mechanism of smooth muscle contraction involving inhibition of PP1- and/or PP2A-activities leading to enhanced force and MLC20-phosphorylation of arterial smooth muscle. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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