Site-specific regulation of ion transport by prolactin in rat colon epithelium

Abstract

The effect of prolactin (PRL) on ion transport across the rat colon epithelium was investigated using Ussing chamber technique. PRL (1 μg/ml) induced a sustained decrease in short-circuit current ( Isc) in the distal colon with an EC50 value of 100 ng/ml and increased Isc in the proximal colon with an EC50 value of 49 ng/ml. In the distal colon, the PRL-induced decrease in Isc was not affected by Na+ channel blocker amiloride or Cl− channel blockers, NPPB, DPC, or DIDS, added mucosally. However, the response was inhibited by mucosal application of K+ channel blockers glibenclamide, quinidine, and chromanol 293B, whereas other K+ channel blockers, Ba2+, tetraethylammonium, clotrimazole, and apamin, failed to have effects. The PRL-induced decrease in Isc was also inhibited by Na+-K+-2Cl− transporter inhibitor bumetanide, Ba2+, and chromanol 293B applied serosally. In the transverse and proximal colon, the PRL-induced increase in Isc was suppressed by DPC, glibenclamide, and bumetanide, but not by NPPB, DIDS, or amiloride. The PRL-induced changes in Isc in both distal and proximal colon were abolished by JAK2 inhibitor AG490, but not BAPTA-AM, the Ca2+ chelating agent, or phosphatidylinositol 3-kinase inhibitor wortmannin. These results suggest a segment-specific effect of PRL in rat colon, by activation of K+ secretion in the distal colon and activation of Cl− secretion in the transverse and proximal colon. Both PRL actions are mediated by JAK-STAT-dependent pathway, but not phosphatidylinositol 3-kinase pathway or Ca2+ mobilization. These findings suggest a role of PRL in the regulation of electrolyte transport in mammalian colon.