Phospholipase A2-activating peptide-induced contraction of smooth muscle is mediated by protein kinase C--MAP kinase cascade.

The mammalian phospholipase A2-activating protein (PLAP) affects of smooth muscle cells isolated from the rabbit rectosigmoid. PLAP (10(6) M)-induced contraction peaked at 30 sec and was sustained at 4 min. MAP kinase was activated by 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 calphostin 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.