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J Smooth Muscle Res. 2019;55(0):14-22. doi: 10.1540/jsmr.55.14.

Inhibitory effects of rubratoxin A, a potent inhibitor of protein phosphatase 2, on the Ca2+-dependent contraction of skinned carotid artery from guinea pig.

Author information

1
Department of Frontier Health Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 7-2-10 Higashiogu, Arakawa-ku, Tokyo 116-8551, Japan.
2
Department of Veterinary Biochemistry, Faculty of Veterinary Medicine, Okayama University of Science, Imabari-shi, Ehime 794-8555, Japan.

Abstract

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 Ca2+-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 Ca2+ concentration. The data fitting to the Hill equation in [Ca2+]-contraction relationship indicated that rubratoxin A decreased Fmax-Ca2+ and increased [Ca2+]50, indices of Ca2+ 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.

KEYWORDS:

Ca2+ sensitivity; contractile proteins; protein phosphatase 2A; rubratoxin A; vascular smooth muscle

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