title: Cyclic AMP and Ca2+-activated K+ transport in a human colonic epithelial cell line.
abstract: Addition of either vasoactive intestinal peptide (VIP) or the Ca2+ ionophore, A23187, to confluent monolayers of the T84 epithelial cell line derived from a human colon carcinoma increased the rate of 86Rb+ or 42K+ efflux from preloaded cells. Stimulation of the rate of efflux by VIP and A23187 still occurred in the presence of ouabain and bumetanide, inhibitors of the Na+,K+-ATPase and Na+,K+,Cl- cotransport, respectively. The effect of A23187 required extracellular Ca2+, while that of VIP correlated with its known effect on cyclic AMP production. Other agents which increased cyclic AMP production or mimicked its effect also increased 86Rb+ efflux. VIP- or A23187-stimulated efflux was inhibited by 5 mM Ba2+ or 1 mM quinidine, but not by 20 mM tetraethylammonium, 4 mM 4-aminopyridine, or 1 microM apamin. Under appropriate conditions, VIP and A23187 also increased the rate of 86Rb+ or 42K+ uptake. Stimulation of the initial rate of uptake by either agent required high intracellular K+ and was not markedly affected by the imposition of transcellular pH gradients. The effect of A23187, but not VIP or dibutyryl cyclic AMP, was refractory to depletion of cellular energy stores. A23187-stimulated uptake was not significantly affected by anion substitution, however, stimulation of uptake by VIP required the presence of a permeant anion. This result may be due to the simultaneous activation of a cyclic AMP-dependent Cl- transport system. The kinetics of both VIP- and A23187-stimulated uptake and efflux were consistent with a channel-rather than a carrier-mediated K+ transport mechanism. The results also suggest that cyclic AMP and Ca2+ may activate two different kinds of K+ transport systems. Finally, both transport systems have been localized to the basolateral membrane of T84 monolayers, a result compatible with their possible regulatory role in hormone-activated electrogenic Cl- secretion.
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000838:Anions; D001464:Barium / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology; D011868:Radioisotopes; D012413:Rubidium / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D000838:Anions; D011868:Radioisotopes; D002034:Bumetanide; D001464:Barium; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D010042:Ouabain; D003994:Bucladesine; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011802:Quinidine; D012413:Rubidium; D011188:Potassium; D002118:Calcium