Inhibitory effects of rubratoxin A, a potent inhibitor of protein phosphatase 2, on the Ca(2+)-dependent contraction of skinned carotid artery from guinea pig

Rubratoxin A, a potent inhibitor of PP2A, is known to suppress smooth muscle contraction. The inhibitory role of PP2A in smooth muscle contraction is still unclear. In order to clarify the regulatory mechanisms of PP2A on vascular smooth muscle contractility, we examined the effects of rubratoxin A on the Ca(2+)-induced contraction of β-escin skinned carotid artery preparations from guinea pigs. Rubratoxin A at 1 µM and 10 µM significantly inhibited skinned carotid artery contraction at any Ca(2+) concentration. The data fitting to the Hill equation in [Ca(2+)]-contraction relationship indicated that rubratoxin A decreased F(max-Ca2+) and increased [Ca(2+)](50), indices of Ca(2+) sensitivity for the force and myosin-actin interaction, respectively. These results suggest that PP2A inhibition causes downregulation of the myosin light chain phosphorylation and direct interference with myosin-actin interaction.