RGD Reference Report - Role of PKC in the novel synergistic action of urotensin II and angiotensin II and in urotensin II-induced vasoconstriction. - Rat Genome Database

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Role of PKC in the novel synergistic action of urotensin II and angiotensin II and in urotensin II-induced vasoconstriction.

Authors: Wang, YX  Ding, YJ  Zhu, YZ  Shi, Y  Yao, T  Zhu, YC 
Citation: Wang YX, etal., Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H348-59. Epub 2006 Sep 1.
RGD ID: 1625607
Pubmed: PMID:16951045   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00512.2006   (Journal Full-text)

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-alpha/betaII 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 microM), the selective PKC-alpha/betaII inhibitor Go-6976 (0.1 and 1 microM), the hU-II receptor ligand urantide (30 nM and 1 microM), or the ANG II antagonist losartan (1 microM). 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 N(G)-nitro-l-arginine methyl ester. hU-II (10 nM) alone caused a long-lasting increase in phospho-PKC-theta, 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 approximately 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-alpha/betaII 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-theta phosphorylation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of vasoconstriction  IEP 1625607 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkcq  (protein kinase C, theta)


Additional Information