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 (I(sc)) in the distal colon with an EC(50) value of 100 ng/ml and increased I(sc) in the proximal colon with an EC(50) value of 49 ng/ml. In the distal colon, the PRL-induced decrease in I(sc) 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, Ba(2+), tetraethylammonium, clotrimazole, and apamin, failed to have effects. The PRL-induced decrease in I(sc) was also inhibited by Na(+)-K(+)-2Cl(-) transporter inhibitor bumetanide, Ba(2+), and chromanol 293B applied serosally. In the transverse and proximal colon, the PRL-induced increase in I(sc) was suppressed by DPC, glibenclamide, and bumetanide, but not by NPPB, DIDS, or amiloride. The PRL-induced changes in I(sc) in both distal and proximal colon were abolished by JAK2 inhibitor AG490, but not BAPTA-AM, the Ca(2+) 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 Ca(2+) mobilization. These findings suggest a role of PRL in the regulation of electrolyte transport in mammalian colon.

Prolactin mediates psychological stress-induced dysfunction of regulatory T cells to facilitate intestinal inflammation

“…Although PRL is not originally found in the intestine, accumulating reports indicate that PRL is involved in a number of intestinal activities, such as modulating the calcium ion movement and altering the epithelial barrier integrity. 32 33 Our data indicate that PRL can also increase the production of IL-6 and IL-23 by DCs in the intestine. Others also found that PRL promoted the DC maturation and played a role in the pathogenesis of immune disorders, such as systemic lupus erythematosus.…”

Prolactin signaling enhances colon cancer stemness by modulating Notch signaling in a Jak2-STAT3/ERK manner

“…PRL and PRLR have been expressed along the gastrointestinal tract in fetal and neonatal stages during development (20). In adult rats, PRL induces active potassium-ion transport in distal colon and chloride-ion transport in proximal and transverse colon (21). IEC-6 colon crypt epithelial cells treated with PRL had increased expression of nutrient and mineral transport channel proteins, without inducing proliferation (22).…”

Use of the Ussing chamber technique to study nutrient transport by epithelial tissues

“…Ussing chambers have been used to study the uptake of glucose, heparin, oligonucleotides, antibiotics and amino acids (7,20,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). The Ussing chamber is an ex vivo technique in which gut tissue is collected and mounted between two buffer-containing reservoirs (luminal and serosal chambers), thus permitting the study of the absorption of compounds across mounted tissues (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”