Dual regulation of heat-stable enterotoxin-mediated cGMP accumulation in T84 cells by receptor desensitization and increased phosphodiesterase activity.
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.
Bakre
M M
MM
Center for Reproductive Biology and Molecular Endocrinology, Indian Institute of Science, Bangalore.
Visweswariah
S S
SS
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D006152:Cyclic GMP / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D020105:Milrinone; D010640:Phenothiazines / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D010640:Phenothiazines; D011688:Purinones; D011728:Pyridones; C034151:heat stable toxin (E coli); D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; C031637:phenothiazine; C011145:zaprinast; D006152:Cyclic GMP; D020105:Milrinone; D015056:1-Methyl-3-isobutylxanthine