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Thapsigargin, a new calcium-dependent epithelial anion secretagogue
D J Brayden1, M R Hanley, O Thastrup
1Department of Pharmacology, University of Cambridge.
British Journal of Pharmacology
|November 1, 1989
Summary
Thapsigargin triggers anion secretion in human colon cells by releasing internal calcium stores. This process requires external calcium and opens channels, aiding chloride efflux and epithelial function studies.
Area of Science:
- Cell Biology
- Gastroenterology
- Ion Transport
Background:
- Electrogenic anion secretion is vital for colonic fluid homeostasis.
- Calcium signaling plays a critical role in regulating epithelial transport.
- Understanding novel secretagogues aids in studying epithelial mechanisms.
Purpose of the Study:
- To investigate the mechanism of thapsigargin-induced anion secretion in human colonic epithelial cells.
- To determine the role of extracellular and intracellular calcium in thapsigargin's effect.
- To explore the interaction of thapsigargin with other secretagogues.
Main Methods:
- Utilized human colonic epithelial cell monolayers.
- Measured electrogenic anion secretion.
- Employed Fura-2 fluorescence to quantify intracellular calcium (Cai) changes.
- Assessed effects of thapsigargin on other secretagogue-induced responses.
Main Results:
- Thapsigargin induced significant anion secretion dependent on external calcium.
- Thapsigargin increased intracellular calcium by releasing internal stores, requiring extracellular calcium for maximal effect.
- Thapsigargin inhibited lysylbradykinin-induced secretion but potentiated cyclic AMP-stimulated responses.
Conclusions:
- Thapsigargin elevates intracellular calcium via non-ionophoric release from internal stores.
- Subsequent calcium influx activates basolateral potassium channels or apical anion channels, promoting chloride efflux.
- Thapsigargin serves as a valuable tool for elucidating epithelial transport mechanisms.