Modulation of chloride secretion in the rat ileum by intracellular bicarbonate.
Increasing intracellular bicarbonate concentration ([HCO3-]i) inhibits calcium-mediated Cl- secretion in rat distal colon and T84 cells. We investigated the effect of [HCO3-]i on Cl- secretion in rat ileum. Segments of intact ileum from Sprague-Dawley rats were studied in Ussing chambers and villus and crypt intracellular pH and [HCO3-]i were determined using BCECF. A range of crypt and villus [HCO3-]i from 0 to 31 mM was obtained by varying Ringer's composition. Basal serosal-to-mucosal Cl- flux (JsmCl) averaged 8.5 +/- 0.2 mu eq.h-1.cm-2 and was unaffected by changing [HCO3-]i or serosal bumetanide. Carbachol increased JsmCl by 3.9 +/- 0.5 mu eq.h-1.cm-2 at [HCO3-]i = 0 mM but only by 1.0 +/- 0.3 mu eq.h-1.cm-2 at high crypt and villus [HCO3-]i. Dibutyryl-cAMP increased JsmCl by 2.5 +/- 0.2 mu eq.h-1.cm-2 at all [HCO3-]i. Carbachol and db-cAMP showed mutual antagonism at low [HCO3-]i and near-additivity at high [HCO3-]i. We conclude that like rat colon and T84 cells, calcium-mediated but not cAMP-mediated Cl- secretion in the ileum is inhibited by increasing [HCO3-]i. Mutual antagonism between carbachol and db-cAMP at low [HCO3-]i was present in ileum and distal colon but not in T84 cells.
Dagher
P C
PC
Nephrology Section, VA Medical Center, New York, NY, USA.
Chawla
H
H
Michael
J
J
Egnor
R W
RW
Charney
A N
AN
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D003994:Bucladesine / Q000378:metabolism; D002217:Carbachol / Q000378:metabolism; D002712:Chlorides / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D005452:Fluoresceins / Q000032:analysis; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007082:Ileum / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D002712:Chlorides; D005452:Fluoresceins; D003994:Bucladesine; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D002217:Carbachol