Three distinct mechanisms of HCO3- secretion in rat distal colon.
HCO(3)(-) secretion has long been recognized in the mammalian colon, but it has not been well characterized. Although most studies of colonic HCO(3)(-) secretion have revealed evidence of lumen Cl(-) dependence, suggesting a role for apical membrane Cl(-)/HCO(3)(-) exchange, direct examination of HCO(3)(-) secretion in isolated crypt from rat distal colon did not identify Cl(-)-dependent HCO(3)(-) secretion but did reveal cAMP-induced, Cl(-)-independent HCO(3)(-) secretion. Studies were therefore initiated to determine the characteristics of HCO(3)(-) secretion in isolated colonic mucosa to identify HCO(3)(-) secretion in both surface and crypt cells. HCO(3)(-) secretion was measured in rat distal colonic mucosa stripped of muscular and serosal layers by using a pH stat technique. Basal HCO(3)(-) secretion (5.6 +/- 0.03 microeq.h(-1).cm(-2)) was abolished by removal of either lumen Cl(-) or bath HCO(3)(-); this Cl(-)-dependent HCO(3)(-) secretion was also inhibited by 100 microM DIDS (0.5 +/- 0.03 microeq.h(-1).cm(-2)) but not by 5-nitro-3-(3-phenylpropyl-amino)benzoic acid (NPPB), a Cl(-) channel blocker. 8-Bromo-cAMP induced Cl(-)-independent HCO(3)(-) secretion (and also inhibited Cl(-)-dependent HCO(3)(-) secretion), which was inhibited by NPPB and by glibenclamide, a CFTR blocker, but not by DIDS. Isobutyrate, a poorly metabolized short-chain fatty acid (SCFA), also induced a Cl(-)-independent, DIDS-insensitive, saturable HCO(3)(-) secretion that was not inhibited by NPPB. Three distinct HCO(3)(-) secretory mechanisms were identified: 1) Cl(-)-dependent secretion associated with apical membrane Cl(-)/HCO(3)(-) exchange, 2) cAMP-induced secretion that was a result of an apical membrane anion channel, and 3) SCFA-dependent secretion associated with an apical membrane SCFA/HCO(3)(-) exchange.
Dept. of Internal Medicine, Yale University, PO Box 208019, New Haven, CT 06520, USA.
Sadasivan
S
Vidyasagar
Vazhaikkurichi M
VM
Rajendran
Henry J
HJ
Binder
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002087:Butyrates / Q000494:pharmacology; D027963:Chloride-Bicarbonate Antiporters / Q000187:drug effects / Q000378:metabolism; D002713:Chlorine; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D058610:Isobutyrates; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D002087:Butyrates; D027963:Chloride-Bicarbonate Antiporters; D058610:Isobutyrates; D002713:Chlorine; C020380:isobutyric acid; D000242:Cyclic AMP; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid