Bicarbonate secretion in rabbit ileum: electrogenicity, ion dependence, and effects of cyclic nucleotides

Gastroenterology. 1993 Dec;105(6):1617-29. doi: 10.1016/0016-5085(93)91056-n.


Background: Ileal HCO3- secretion is not well understood. The aim of this study was to examine its Na+ and Cl- dependencies, electrogenicity, and responses to amiloride, 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonate (SITS), and cyclic nucleotides.

Methods: The serosa to mucosa HCO3- flux (Jsm) across rabbit ileal mucosa mounted between HCO(3-)-free mucosal solution and HCO(3-)-containing serosal solutions was determined by titration.

Results: In SO4(2-)-containing Ringer's solution, Jsm varied with [Na+] in two phases, one with a high and one with a low affinity for Na+; amiloride inhibited the high- and SITS inhibited the low-affinity phase. Switching from SO4(2-)- to Cl(-)-containing Ringer's solution caused a SITS-inhibitable 42% increase in Jsm. Changes in Jsm were coupled 3:2 with changes in short-circuit current. Cyclic nucleotide effects on Jsm were as follows. In SO4(2-)-containing Ringer's solution at 141 (but not 80) mmol/L Na+, theophylline caused equal increases in Jsm and short-circuit current that equaled the combined effects of 8-Br-5'-cyclic guanosine monophosphate (cGMP) and 8-Br-5'-cyclic adenosine monophosphate (cAMP). Serosal SITS blocked these effects, but amiloride did not. In Cl(-)-containing Ringer's solution, theophylline and bumetanide together (but not separately) increased Jsm.

Conclusions: (1) Basolateral HCO3- entry occurs via Na+/H exchange and a SITS-inhibitable process (Na(+)-HCO3- cotransport?). (2) Most HCO3- exit across the brush border occurs by a Cl(-)-independent process and some by Cl-/HCO3- exchange. (3) At low cellular [Cl-], HCO3- can be secreted via anion channels activated by cAMP and cGMP. (4) Ileal HCO3- secretion is electrogenic.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / pharmacology
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology*
  • Amiloride / pharmacology
  • Animals
  • Bicarbonates / metabolism*
  • Bumetanide / pharmacology
  • Chlorides / metabolism
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / pharmacology
  • Ethoxzolamide / pharmacology
  • Ileum / drug effects
  • Ileum / metabolism*
  • In Vitro Techniques
  • Male
  • Rabbits
  • Sodium / metabolism
  • Theophylline / pharmacology


  • Bicarbonates
  • Chlorides
  • Bumetanide
  • 8-Bromo Cyclic Adenosine Monophosphate
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid
  • 8-bromocyclic GMP
  • Amiloride
  • Sodium
  • Theophylline
  • Cyclic GMP
  • Ethoxzolamide