Endothelin-1 induced sustained contractions of tracheal smooth muscle involve an activation of protein kinase C

摘要

Endothelin-1, a potent vasoconstrictor peptide produces concentration dependent contractions in lamb tracheal smooth muscle. These contractions are not inhibited by low doses (up to 20 μM) of trifluoroperazine and W-7, the calmodulin/myosin light chain kinase (MLCK) inhibitors. At higher concentrations (200 μM), a delayed and poor reversal of isometric tensions results. These relaxations are coupled with a partial dephosphorylation of regulatory myosin light chain (MLC). Preincubation of fiber strips in MLCK inhibitors (200 μM) results in a delayed and attenuated contractile response but without a dephosphorylation of M LC. H-7, a putative protein kinase C antagonist (25-100 μM) abolishes endothelin-1 induced contractile effects rapidly (50/100 relaxation within 1-3 min).