Ba2+ inhibition of VIP- and A23187-stimulated Cl- secretion by T84 cell monolayers.
Addition of either 10(-8) M vasoactive intestinal polypeptide (VIP) or 10(-6) M A23187 to T84 cell monolayers, grown on permeable supports and mounted in Ussing chambers, stimulated net Cl- secretion. The effect of 10(-6) M A23187 on Cl- flux was consistently smaller than that observed with 10(-8) M VIP. In both cases the increase in net Cl- secretion accounted for the entire change in the observed short-circuit current (Isc). Since Cl- enters the cells through a basolaterally localized Na+-K+-Cl(-)-cotransport system (J. Clin. Invest. 75: 462, 1985), the fate of K+, which is cotransported with Cl- during VIP, and A23187-mediated Cl- secretion was explored. Unidirectional and net transepithelial 42K+ flux rates were negligible compared with 36Cl- flux rates (less than 4% of Cl- flux), indicating that little K+ was secreted along with Cl-. K+ recycling across the basolateral membrane was suggested from experiments in which 86Rb+ efflux (as a tracer for K+) was measured across the apical and basolateral membranes of 86Rb+ -preloaded monolayers under voltage-clamped conditions. In the absence of secretagogues, 86Rb+ efflux was 10-fold higher across the basolateral membrane than across the apical membrane. 86Rb+ efflux across the basolateral membrane was accelerated two- to threefold by addition of either VIP or A23187. In each case accelerated efflux was inhibited by 5 mM Ba2+. Cl- secretion induced by VIP or A23187 was also inhibited by serosal addition of Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)
K G
KG
Mandel
J A
JA
McRoberts
G
G
Beuerlein
E S
ES
Foster
K
K
Dharmsathaphorn
D001464:Barium / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011868:Radioisotopes; D012413:Rubidium; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002712:Chlorides; D007473:Ion Channels; D011868:Radioisotopes; D001464:Barium; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D012964:Sodium; D012413:Rubidium; D011188:Potassium