HCO(3)(-) secretion in the rat colonic crypt is closely linked to Cl(-) secretion.
OBJECTIVE
The mechanism of colonic HCO(3)(-) secretion has not been established largely because of a lack of experimental methods for its detailed study. The present studies were designed to establish whether the isolated, perfused crypt of the rat distal colon is an excellent model to study HCO(3)(-) movement and the mechanism of colonic HCO(3)(-) secretion.


METHODS
HCO(3)(-) secretion was determined in isolated, microperfused crypts by measuring [HCO(3)(-)] by microcalorimetry on nanoliter samples.


RESULTS
Net HCO(3)(-) absorption was observed during lumen and bath perfusion with an HCO(3)(-)-Ringer solution. Vasoactive intestinal polypeptide (60 nmol/L), acetylcholine (100 nmol/L), or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 0.5 mmol/L) induced active HCO(3)(-) secretion that required bath but not lumen HCO(3)(-)/CO(2). DBcAMP-stimulated HCO(3)(-) secretion was not affected by acetazolamide, an inhibitor of carbonic anhydrase. Removal of lumen Cl(-) did not alter DBcAMP-stimulated HCO(3)(-) secretion but reduced fluid secretion. DBcAMP-stimulated HCO(3)(-) secretion was closely linked to active Cl(-) secretion because HCO(3)(-) secretion was substantially reduced by removal of bath Cl(-), by addition of bath bumetanide, an inhibitor of Na-K-2Cl cotransport and Cl(-) secretion, and by addition of lumen NPPB, a Cl(-) channel inhibitor.


CONCLUSIONS
These studies establish that colonic crypt HCO(3)(-) secretion (1) is not a result of an apical membrane Cl(-)-HCO(3)(-) exchange, (2) is tightly associated with Cl(-) secretion, and (3) primarily occurs via an apical membrane Cl(-) channel.
Geibel
J P
JP
Department of Surgery, Yale University, New Haven, Connecticut 06520-8019, USA.
Singh
S
S
Rajendran
V M
VM
Binder
H J
HJ
D000042:Absorption; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D066298:In Vitro Techniques; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D001639:Bicarbonates; D002712:Chlorides; D014660:Vasoactive Intestinal Peptide; D003994:Bucladesine; D000109:Acetylcholine