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Title: Role of PKC in the novel synergistic action of urotensin II and angiotensin II and in urotensin II-induced vasoconstriction
Authors: Wang, Y.-X.
Ding, Y.-J.
Zhu, Y.-Z. 
Shi, Y.
Yao, T.
Zhu, Y.-C.
Keywords: Protein kinase C
Vascular smooth muscle cells
Issue Date: Jan-2007
Citation: Wang, Y.-X., Ding, Y.-J., Zhu, Y.-Z., Shi, Y., Yao, T., Zhu, Y.-C. (2007-01). Role of PKC in the novel synergistic action of urotensin II and angiotensin II and in urotensin II-induced vasoconstriction. American Journal of Physiology - Heart and Circulatory Physiology 292 (1) : H348-H359. ScholarBank@NUS Repository.
Abstract: The intracellular signaling of human urotensin II (hU-II) and its interaction with other vasoconstrictors such as ANG II are poorly understood. In endothelium-denuded rat aorta, coadministration of hU-II (1 nM) and ANG II (2 nM) exerted a significant contractile effect that was associated with increased protein kinase C (PKC) activity and phosphorylation of PKC-α/βII and myosin light chain, whereas either hU-II or ANG II administered alone at these concentrations had no statistically significant effect. This synergistic effect was abrogated by the PKC inhibitor chelerythrine (10 and 30 μM), the selective PKC-α/βII inhibitor Gö-6976 (0.1 and 1 μM), the hU-II receptor ligand urantide (30 nM and 1 μM), or the ANG II antagonist losartan (1 μM). Moreover, in endothelium-intact rat aorta, the synergistic effect of hU-II and ANG II was not exerted any longer, and this synergistic effect was unmasked by pretreatment of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. hU-II (10 nM) alone caused a long-lasting increase in phospho-PKC-θ, phospho-myosin light chain, and PKC activity, which was associated with long-lasting vasoconstriction. These changes were prevented by chelerythrine. Methoxyverapamil-thapsigargin treatment reduced the hU-II-induced vasoconstriction by ∼50%. The methoxyverapamil-thapsigargin-resistant component of hU-II-induced vasoconstriction was dose-dependently inhibited by chelerythrine. In conclusion, hU-II induces a novel PKC-dependent synergistic action with ANG II in inducing vasoconstriction. PKC-α/βII is probably the PKC isoform involved in this synergistic action. Nitric oxide produced in the endothelium probably masks this synergistic action. The long-lasting vasoconstriction induced by hU-II alone is PKC dependent and associated with PKC-θ phosphorylation. Copyright © 2007 the American Physiological Society.
Source Title: American Journal of Physiology - Heart and Circulatory Physiology
ISSN: 03636135
DOI: 10.1152/ajpheart.00512.2006
Appears in Collections:Staff Publications

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