Modulation of secretagogue-induced chloride secretion by intracellular bicarbonate.
We have previously demonstrated inhibition of basal Cl- secretion by intracellular bicarbonate concentration ([HCO3-]i) in rat distal colon. We now examined whether secretagogue-induced Cl- secretion is inhibited by [HCO3-]i as well. Stripped segments of distal colon from male Sprague-Dawley rats and the colon tumor cell line T84 were studied. Flux measurements were performed in the Ussing chamber under short-circuit conditions. [HCO3-]i was calculated from intracellular pH (pHi) values that were estimated with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and carbachol were used as secretagogues. In both distal colon and T84 cells, [HCO3-]i did not affect cAMP-induced Cl- secretion. However, carbachol-induced secretion was inhibited by [HCO3-]i; in rat colon, Cl- secretion decreased from 2.3 to 1.5 mueq.cm-2.h-1 when [HCO3-]i was increased from 15.0 to 28.4 mM (P < 0.05). In T84 cells, the change in short-circuit current decreased from 8.1 to 1.1 microA/cm2 over a range of [HCO3-]i from 0 to 15.6 mM (P < 0.001). We conclude that [HCO3-]i is an important modulator of carbachol-stimulated Cl- secretion in both rat distal colon and the T84 cell line. cAMP-mediated secretion is not affected by [HCO3-]i.
Dagher
P C
PC
Nephrology Section, Department of Veterans Affairs Medical Center, New York University School of Medicine, New York 10010.
Morton
T Z
TZ
Joo
C S
CS
Taglietta-Kohlbrecher
A
A
Egnor
R W
RW
Charney
A N
AN
D000704:Analysis of Variance; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003110:Colonic Neoplasms; D000242:Cyclic AMP / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
D001639:Bicarbonates; D002712:Chlorides; D003994:Bucladesine; D002217:Carbachol; D000242:Cyclic AMP