The present study investigated the segmental discrepancy of the rat distal colonic anion transport induced by luminal forskolin and the possible underlying mechanisms using short-circuit current recording technique and comparative quantity real-time PCR analysis. Forskolin-induced
ISC in the segment next to lymph node (DC
1) and the segment 4 cm away from lymph node (DC
4) were 4.09±0.66 μA/cm
2 and 18.84±3.18 μA/cm
2 (
n=13), respectively, which were blocked by luminal Cl
− channel blocker, glybenclamide (1 m
M) (
n=5,
p<0.01), as well as removal of extracellular Cl
− and HCO
3− in both DC
1 and DC
4 (
n=5,
p<0.001). Furthermore luminal pretreatment with K
+ blockers, TEA (5 m
M) and glybenclamide (100 μ
M) didn't affect forskolin and bumetanide-enhanced
ISC. Reducing serosal Cl
− concentration increased forskolin-induced
ISC by 90% in DC
1 but decreased forskolin-induced
ISC in DC
4 by 50%. Furthermore, pretreatment with serosal bumetanide, an inhibitor of Na
+-K
+-2Cl
− cotransporter, enhanced forskolin-induced
ISC by 87% in DC
1, from 4.09±0.66 μA/cm
2 to 7.65±0.53 μA/cm
2 (
n=6,
p<0.01), but inhibited forskolin-induced
ISC by 50% in DC
4, from 29.19±4.51 μA/cm
2 to 15.06±4.10 μA/cm
2 (
n=6,
p<0.05). Pretreatment with luminal amiloride (10 μ
M), an inhibitor of ENaC, and serosal 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) (200 μ
M), an inhibitor of NBC, significantly inhibited the forskolin-induced
ISC in DC
1 (
n=6,
p<0.05), but not in DC
4. Real-time PCR analysis did not show the significant differences between the two segments in the expression amounts of CFTR and NKCC mRNAs, however the expression of NBC mRNA in DC
4 was significantly higher than that in DC
1. In conclusion, the rat distal colon manifests a segmental discrepancy in anion transport stimulated by luminal forskolin. HCO
3− might be predominantly involved in the forskolin-induced anion secretion in DC
1, but Cl
− might be the main component of the anion secretion in DC
4.
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