Mechanisms by which cyclic nucleotides and other intracellular mediators regulate secretion.
The regulation of Na+ and Cl- transport across surface membranes and tight junctions of intestinal epithelium is mediated through at least three intracellular messengers: (i) 3',5'-cyclic AMP, activating two types of cyclic AMP-dependent protein kinase, (ii) 3',5'-cyclic GMP, binding to a unique isoenzyme of cyclic GMP-dependent protein kinase, enriched in the intestinal brush border, and (iii) Ca2+ ions, partially acting through calmodulin and a Ca2+/phospholipid-dependent protein kinase (C kinase). Recent data on the subcellular distribution and molecular properties of the high affinity cyclic nucleotide and Ca2+ receptors, their influence on the phosphorylation state of specific membrane proteins, and the possible role of these target proteins in ion transport regulation, are reviewed. The following aspects are accentuated: (1) the asymmetrical compartmentation of cyclic AMP-dependent protein kinase isoenzymes in the enterocyte and its functional implications; (2) the structure and function of microvillous cyclic GMP-dependent protein kinase; (3) the integration of cyclic AMP and cyclic GMP signals through co-phosphorylation of a 25 000 Mr protein in the intestinal-microvilli; (4) the identification of C kinase in villous and crypt cells; (5) various levels of interaction between cyclic nucleotide and Ca2+ signals; and (6) priority areas for future studies on stimulus-secretion coupling.
H R
HR
de Jonge
S M
SM
Lohmann
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D012964:Sodium; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D011188:Potassium