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.
Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109-0658, USA.
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D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D011817:Rabbits
D011506:Proteins; C055324:phospholipase A2-activating protein; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins