Control of Ion Transport in Mouse Proximal and Distal Colon by Prolactin

Abstract

The lactogenic hormone prolactin (PRL) has been known to affect Ca²⁺ and electrolyte transport in the intestinal epithelium. In the present study we analyzed ion transport in mouse proximal and distal colon, and acute changes induced by PRL. In the proximal colon, carbachol activated a Ca²⁺ dependent Cl^- secretion that was sensitive to DIDS and NFA. In the distal colon, both ATP and carbachol activated K⁺ secretion. Ca²⁺ -activated KCl transport in proximal and distal colon was inhibited by PRL (200ng/ml), while amiloride sensitive Na⁺ absorption and cAMP induced Cl^- secretion remained unaffected. Luminal large conductance Ca²⁺ -activated K⁺ (BK) channels were largely responsible for Ca²⁺ -activated K⁺ secretion in the distal colon, and basolateral BK channels supported Ca²⁺ -activated Cl^- secretion in the proximal colon. Ca²⁺ chelating by BAPTA-AM attenuated effects of carbachol and abolished effects of PRL. Both inhibition of PI3 kinase with wortmannin and blockage of MAP kinases with SB 203580 or U 0126, interfered with the acute inhibitory effect of PRL on ion transport, while blocking of Jak/Stat kinases with AG 490 was without effects. PRL attenuated the increase in intracellular Ca²⁺ that was caused by stimulation of isolated colonic crypts with carbachol. Thus PRL inhibits Ca²⁺ dependent Cl^- and K⁺ secretion by interfering with intracellular Ca²⁺ signaling and probably by activating PI3 kinase and MAP kinase pathways.