Normal Mucus Release Requires Both Ca2+‐mediated Exocytosis and cAMP Mediated HCO3‐ Transport

Abstract

Mounting evidence indicates that the formation of normal mucus depends critically on the environment into which it is discharged. We applied histology, Ussing chamber pH-stat assays, and mucus collection methods to examine the links between mucin release and ion transport. In wild type mouse (C57BL/6) small intestine, the Ca2+ mediated agonist (carbachol) did not stimulate sustained HCO3− secretion, but induced mucin exocytosis (histologically) and a short circuit current (Isc) increase (possibly due to Cl− secretion). In contrast, cAMP mediated agonists (vasoactive intestinal peptide, isoproterenol) induced both HCO3− secretion and Isc increase, but little, if any, exocytosis. cAMP mediated agonists combined with carbachol discharged more mucus into the luminal perfusate than carbachol alone, but the cAMP enhancing effect was absent without HCO3−. In CF (ΔF508/ΔF508) mouse small intestine, neither Ca2+ nor cAMP mediated agonists induced significant HCO3− secretion, Isc increase or significant mucus discharge. These results indicate that normal mucus release requires Ca2+ mediated exocytosis, possibly Cl− secretion, and apparently post-exocytotic cAMP-mediated HCO3− secretion to affect normal mucin discharge. Concept: Mucus discharge requires Ca2+ mediated exocytosis + cAMP mediated HCO3− secretion. We thank the CFRI, CF Foundation, NIH-RO1 HL084042 and Dr. Hui Dong.