Okadaic acid increases the phosphorylation state of alpha1A-adrenoceptors and induces receptor desensitization
- PMID: 16297906
- DOI: 10.1016/j.ejphar.2005.09.057
Okadaic acid increases the phosphorylation state of alpha1A-adrenoceptors and induces receptor desensitization
Abstract
Okadaic acid, a protein phosphatase inhibitor, and phorbol myristate acetate, an activator of protein kinase C, increased the phosphorylation state of alpha1A-adrenergic receptors. The effects of these agents were of similar magnitude but that of okadaic acid developed more slowly. Wortmannin (inhibitor of phosphoinositide 3-kinase), but not staurosporine (inhibitor of protein kinase C), abolished the effect of okadaic acid on the alpha1A-adrenoceptor phosphorylation state. The effect of phorbol myristate acetate on this parameter was blocked by staurosporine and only partially inhibited by wortmannin. Okadaic acid markedly increased the co-immunoprecipitation of both the catalytic and regulatory subunits of phosphatidylinositol 3-kinase and of Akt/protein kinase B with the adrenoceptor and only marginally increases receptor association with protein kinase C epsilon. Okadaic acid induced desensitization of alpha1A-adrenoceptors as evidenced by a decreased ability of noradrenaline to increase intracellular calcium. Such desensitization was fully reverted by wortmannin. Our data indicate that inhibition of serine/threonine protein phosphatases increases the phosphorylation state of alpha1A-adrenergic receptor and alters the adrenoceptor function.
Similar articles
-
Protein phosphatase-protein kinase interplay modulates alpha 1b-adrenoceptor phosphorylation: effects of okadaic acid.Br J Pharmacol. 2000 Feb;129(4):724-30. doi: 10.1038/sj.bjp.0703073. Br J Pharmacol. 2000. PMID: 10683197 Free PMC article.
-
Receptor tyrosine kinases regulate alpha1D-adrenoceptor signaling properties: phosphorylation and desensitization.Int J Biochem Cell Biol. 2009 Jun;41(6):1276-83. doi: 10.1016/j.biocel.2008.10.030. Epub 2008 Nov 6. Int J Biochem Cell Biol. 2009. PMID: 19038360
-
Lysophosphatidic acid modulates alpha(1b)-adrenoceptor phosphorylation and function: roles of Gi and phosphoinositide 3-kinase.Mol Pharmacol. 2000 May;57(5):1027-33. Mol Pharmacol. 2000. PMID: 10779388
-
The use of okadaic acid to elucidate the intracellular role(s) of protein phosphatase 2A: lessons from the mast cell model system.Int Immunopharmacol. 2005 Sep;5(10):1507-18. doi: 10.1016/j.intimp.2005.05.007. Int Immunopharmacol. 2005. PMID: 16023602 Review.
-
[Alpha 1B-adrenoceptor phosphorylation or desensitization].Sheng Li Ke Xue Jin Zhan. 2003 Jul;34(3):251-4. Sheng Li Ke Xue Jin Zhan. 2003. PMID: 14628475 Review. Chinese. No abstract available.
Cited by
-
The relationship between the MMP system, adrenoceptors and phosphoprotein phosphatases.Br J Pharmacol. 2012 Jun;166(4):1225-43. doi: 10.1111/j.1476-5381.2012.01917.x. Br J Pharmacol. 2012. PMID: 22364165 Free PMC article. Review.
-
Location, location, location...site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling.Trends Pharmacol Sci. 2008 Aug;29(8):413-20. doi: 10.1016/j.tips.2008.05.006. Epub 2008 Jul 6. Trends Pharmacol Sci. 2008. PMID: 18606460 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
