Phospholipase A2-Activating Peptide Induced Contraction of Smooth Muscle Is Mediated by Protein Kinase C-MAP Kinase Cascade

Abstract

The mammalian phospholipase A2-activating protein (PLAP) affects contraction of smooth muscle cells isolated from the rabbit rectdyosigmoid. PLAP (10−6 M), as measured using myelin basic protein (MBP) as substrate. The increase in MAP kinase activity was rapid at 30 sec (159±2.5%) and remained at a sustained level (162±7.9%) at 4 min. Preincubation of the cells with the PLA2 inhibitor ONO-RS-082 (10−6 M) or with the PKC inhibitor calphostic C (10−6 M) resulted in inhibition of contraction, as well as inhibition of the associated increase in MAP kinase activation. The data indicates that PLAP-specific contractile effect on isolated smooth muscle cells is mediated by an activation of a PKC-MAP kinase cascade and suggests a putative role for PLA2-coupled G protein activation of PKC-MAP kinase as an alternate transduction pathway in smooth muscle contraction.