"Store-operated" cAMP signaling contributes to Ca2+-activated Cl- secretion in T84 colonic cells

American Journal of Physiology. Gastrointestinal and Liver Physiology
Jonathan M NicholsAldebaran M Hofer

Abstract

Apical cAMP-dependent CFTR Cl(-) channels are essential for efficient vectorial movement of ions and fluid into the lumen of the colon. It is well known that Ca(2+)-mobilizing agonists also stimulate colonic anion secretion. However, CFTR is apparently not activated directly by Ca(2+), and the existence of apical Ca(2+)-dependent Cl(-) channels in the native colonic epithelium is controversial, leaving the identity of the Ca(2+)-activated component unresolved. We recently showed that decreasing free Ca(2+) concentration ([Ca(2+)]) within the endoplasmic reticulum (ER) lumen elicits a rise in intracellular cAMP. This process, which we termed "store-operated cAMP signaling" (SOcAMPS), requires the luminal ER Ca(2+) sensor STIM1 and does not depend on changes in cytosolic Ca(2+). Here we assessed the degree to which SOcAMPS participates in Ca(2+)-activated Cl(-) transport as measured by transepithelial short-circuit current (Isc) in polarized T84 monolayers in parallel with imaging of cAMP and PKA activity using fluorescence resonance energy transfer (FRET)-based reporters in single cells. In Ca(2+)-free conditions, the Ca(2+)-releasing agonist carbachol and Ca(2+) ionophore increased Isc, cAMP, and PKA activity. These responses p...Continue Reading

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Oct 3, 2018·Critical Reviews in Food Science and Nutrition·Maria Del Carmen Ponce de León-RodríguezCaroline Laurent-Babot
Jun 8, 2017·Frontiers in Cellular and Infection Microbiology·Rachid A El-Aouar FilhoNadia Berkova
Oct 1, 2017·Scientific Reports·Roberta BenedettoKarl Kunzelmann
Aug 20, 2021·Toxicon : Official Journal of the International Society on Toxinology·Leila Staali, Didier A Colin

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