Dopamine stimulates Cl− absorption coupled with HCO3− secretion in rat late distal colon

Freshly isolated rat colonic mucosa close to anus (the late distal colonic mucosa) was used to investigate the effect of dopamine on the rat late distal colonic ion transport by means of short-circuit current (ISC) recording and reverse transcription PCR (RT-PCR) analysis. The results showed that the basolateral addition of dopamine (0.1–1000 μmol/l) produced a concentration-dependent downward deflection in ISC with an apparent EC50 of 20.06 μmol/l in the late distal colon. The dopamine-induced ISC decrease was abolished by bilateral removal of Cl− or HCO3−, apical Cl− replacement and apical pretreatment with non-specific Cl− channel blocker/transporter inhibitor, DPC (1 mmol/l) or glibenclamide (1 mmol/l), and reversed by subsequent addition of glibenclamide. Removal of basolateral Na+ or reducing basolateral HCO3− (3 mmol/l) as well as basolateral pretreatment with DIDS (4,4′-didsothio- cyanostilbene-2, 2′-disulfonic acid) (250 μmol/l), an inhibitor of NBC or AE, could also inhibit the dopamine-induced ISC response. However, apical pretreatment with epithelial Na+ channel blocker, amiloride (10 μmol/l), Ca2+-dependent Cl− channel blocker/anion exchanger, DIDS (100 μmol/l), or putative K+ blockers such as Ba2+ (5 mmol/l), TEA (tetraethylammonium) (5 mmol/l) or 293B (trans-6-cyano-4- (N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane) (10 μmol/l) did not significantly affect the dopamine-induced ISC response. RT-PCR results showed the expression of anion exchanger, SLC26A3, but not SLC26A6, in rat late distal colon. In conclusion, the present results suggest that dopamine may promote rat late distal colonic epithelial Cl− absorption coupled with HCO3− secretion, which may be mediated by apical electrogenic anion exchanger, SLC26A3, and require basolateral entry of HCO3− through Na+-HCO3− cotransporter. The present findings reveal a previously unreported dopamine-regulated anion transport process in rat late distal colon, which may have implication in Parkinson's disease.