ArticleProceedings of the National Academy of Sciences of the United States of America1995
Extracellular pH regulation in microdomains of colonic crypts: effects of short-chain fatty acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine.Journal of molecular cell biology · 2024Article
- Mechanisms of proton pump inhibitor-induced hypomagnesemia.Acta physiologica (Oxford, England) · 2022Review
- Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022Review
- Fecal Microbiota Transplantation Donor and Dietary Fiber Intervention Collectively Contribute to Gut Health in a Mouse Model.Frontiers in immunology · 2022Article
- Butyrate Protects Porcine Colon Epithelium from Hypoxia-Induced Damage on a Functional Level.Nutrients · 2021Article
- Extracellular protons enable activation of the calcium-dependent chloride channel TMEM16A.The Journal of physiology · 2017Article
- The metabolic fate of acetate in cancer.Nature reviews. Cancer · 2016Review
- The use of murine-derived fundic organoids in studies of gastric physiology.The Journal of physiology · 2015Article
- Epithelial cell proliferation arrest induced by lactate and acetate from Lactobacillus casei and Bifidobacterium breve.PloS one · 2013Article
- Extracellular pH regulates zinc signaling via an Asp residue of the zinc-sensing receptor (ZnR/GPR39).The Journal of biological chemistry · 2012Article
- Functional Cftr in crypt epithelium of organotypic enteroid cultures from murine small intestine.American journal of physiology. Cell physiology · 2012Article
- Ischemic post-conditioning to counteract intestinal ischemia/reperfusion injury.World journal of gastrointestinal pathophysiology · 2010Article
- A genetically encoded ratiometric sensor to measure extracellular pH in microdomains bounded by basolateral membranes of epithelial cells.Pflugers Archiv : European journal of physiology · 2008Article
- pH gradients and a micro-pore filter at the luminal surface affect fluxes of propionic acid across guinea pig large intestine.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2007Article
- Article
- Cellular mechanisms for apical ATP effects on intracellular pH in human bronchial epithelium.The Journal of physiology · 2002Article
- A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
- Short chain fatty acids differentially modulate cellular phenotype and c-myc protein levels in primary human nonmalignant and malignant colonocytes.Digestive diseases and sciences · 2001Article
- H(+)/solute-induced intracellular acidification leads to selective activation of apical Na(+)/H(+) exchange in human intestinal epithelial cells.The Journal of clinical investigation · 1999Article
- Maintenance and regulation of the pH microclimate at the luminal surface of the distal colon of guinea-pig.The Journal of physiology · 1999Article
Corrections and comments
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2 authors.
Funding
Abstract
It has been suggested that transepithelial gradients of short-chain fatty acids (SCFAs; the major anions in the colonic lumen) generate pH gradients across the colonic epithelium. Quantitative confocal microscopy was used to study extracellular pH in mouse distal colon with intact epithelial architecture, by superfusing tissue with carboxy SNARF-1 (a pH-sensitive fluorescent dye). Results demonstrate extracellular pH regulation in two separate microdomains surrounding colonic crypts: the crypt lumen and the subepithelial tissue adjacent to crypt colonocytes. Apical superfusion with (i) a poorly metabolized SCFA (isobutyrate), (ii) an avidly metabolized SCFA (n-butyrate), or (iii) a physiologic mixture of acetate/propionate/n-butyrate produced similar results: alkalinization of the crypt lumen and acidification of subepithelial tissue. Effects were (i) dependent on the presence and orientation of a transepithelial SCFA gradient, (ii) not observed with gluconate substitution, and (iii) required activation of sustained vectorial acid/base transport by SCFAs. Results suggest that the crypt lumen functions as a pH microdomain due to slow mixing with bulk superfusates and that crypts contribute significant buffering capacity to the lumen. In conclusion, physiologic SCFA gradients cause polarized extracellular pH regulation because epithelial architecture and vectorial transport synergize to establish regulated microenvironments.
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