Dual regulation of heat-stable enterotoxin-mediated cGMP accumulation in T84 cells by receptor desensitization and increased phosphodiesterase activity

FEBS Letters
M M Bakre, Sandhya S Visweswariah

Abstract

We report the regulation of cGMP accumulation induced by the heat-stable enterotoxin, STh, in the T84 human colonic cell line. STh binding to its receptor, guanylyl cyclase C (GCC), leads to elevated intracellular levels of cGMP. Prolonged exposure of T84 cells to STh induced refractoriness to further cGMP accumulation, without significant receptor internalization, but with reduced STh-induced cGMP synthesis by the receptor. Significantly, increased degradation of cGMP by a cGMP-specific phosphodiesterase was observed in desensitized cells. This is the first report on the desensitization of GCC, as well as the role of the Type V phosphodiesterase in inducing cellular refractoriness.

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Citations

Mar 30, 2001·European Journal of Biochemistry·N RoyS S Visweswariah
Jul 22, 2009·Molecular and Cellular Biology·Nirmalya BasuSandhya S Visweswariah
Feb 16, 2005·Annual Review of Physiology·John P Geibel
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·G M PitariS A Waldman
May 13, 1999·The Journal of Biological Chemistry·J D Corbin, S H Francis
Sep 6, 2013·Microbiology and Molecular Biology Reviews : MMBR·Vanessa Liévin-Le Moal, Alain L Servin
Dec 5, 2009·Molecular and Cellular Biochemistry·Nirmalya BasuSandhya S Visweswariah

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