Regulation of human Caco-2 intestinal epithelial brush border enzyme activity by cyclic nucleotides.
Regulation of intestinal epithelial differentiation is critical to normal function, malignant transformation, and healing. However, the intracellular regulation of intestinal epithelial differentiation is incompletely understood. We studied the effects of intracellular cyclic AMP and cyclic GMP on brush border enzyme activity in the human Caco-2 intestinal epithelial cell using pharmacologic agonists and antagonists of cAMP and cGMP mediated pathways as probes. The stable cyclic nucleotide analogs dibutyryl cAMP and dibutyryl cGMP selectively decreased Caco-2 dipeptidyl dipeptidase specific activity while increasing alkaline phosphatase. The inhibitors of adenylate and guanylate cyclase KT5720 and KT5823 each exerted the opposite effects. Combinations of dibutyryl cAMP and dibutyryl cGMP demonstrated synergistic effects on each brush border enzyme but KT5720 and KT5823 were less than additive. Thus, cAMP and CGMP may regulate human intestinal epithelial differentiation by interacting pathways.
Basson
M D
MD
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA.
Hong
F
F
D000067956:Adenylyl Cyclase Inhibitors; D000469:Alkaline Phosphatase / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology*; D018938:Caco-2 Cells; D002227:Carbazoles; D002460:Cell Line; D003110:Colonic Neoplasms; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006706:Homeostasis; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007422:Intestines; D007700:Kinetics; D008871:Microvilli / Q000201:enzymology*; D011758:Pyrroles / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; C073601:KT 5823; D003995:Dibutyryl Cyclic GMP; C057416:KT 5720; D003994:Bucladesine; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D006162:Guanylate Cyclase; D006152:Cyclic GMP