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

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.

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.

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.

(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.