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Emodin inhibits tonic tension through suppressing PKCδ-mediated inhibition of myosin phosphatase in rat isolated thoracic aorta.

Br. J. Pharmacol.2014 Sep;171(18):4300-10. doi:10.1111/bph.12804
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摘要


BACKGROUND AND PURPOSE:Dysregulated tonic tension and calcium sensitization in blood vessels has frequently been observed in many cardiovascular diseases. Despite a huge therapeutic potential, little is known about natural products targeting tonic tension and calcium sensitization. EXPERIMENTAL APPROACH:We screened natural products for inhibitory effects on vasoconstriction using the rat isolated thoracic aorta and found that an anthraquinone derivative, emodin, attenuated tonic tension. Organ bath system, primary vascular smooth muscle cells, confocal microscopy and Western blot analysis were employed to demonstrate the suppressive effects of emodin on myosin phosphatase inhibition. KEY RESULTS:Emodin, an active ingredient of Polygonum multiflorum extract, inhibited phenylephrine-induced vasoconstriction in rat isolated thoracic aorta, and inhibited vasoconstriction induced by 5-HT and endothelin-1. It also generally suppressed vasoconstrictions mediated by voltage-operated, store-operated calcium channels and intracellular calcium store. However, emodin did not affect agonist-induced calcium increases in primary smooth muscle cells. In contrast, post-treatment with emodin following phenylephrine stimulation potently suppressed tonic tension in rat aortic rings. Western blot analysis revealed that emodin inhibited phenylephrine-induced phospho-myosin light chain (pMLC) and the phosphorylation of myosin-targeting subunit and C-kinase-activated protein phosphatase-1 inhibitor (CPI-17). This was mediated by selective inhibition of whereas was not involved. CONCLUSION AND IMPLICATIONS:Emodin attenuates tonic tension through the blockade of and CPI-17-mediated MLC-phosphatase inhibition. This new mode of action for the suppression of tonic tension and structural insights into duanyu1531δ inhibition revealed by emodin may provide new information for the development of modulators of tonic tension and for the treatment of hypertension.

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