Thapsigargin, a new calcium-dependent epithelial anion secretagogue

British Journal of Pharmacology
D J BraydenA W Cuthbert

Abstract

1. Thapsigargin, a sesquiterpene lactone, was shown to cause electrogenic anion secretion in monolayers of human colonic epithelial cells, an effect which was crucially dependent upon calcium and did not involve eicosanoid formation. 2. To measure the secretory effect calcium needed to be present in the external bathing solution. By means of Fura-2 fluorescence measurements thapsigargin was shown to raise Cai by around 250 nM when the bathing solution contained calcium. In the nominal absence of external calcium thapsigargin raised Cai by only 60 nM, but from a lower basal value. This was insufficient to cause secretion. 3. Effects of other calcium-dependent secretagogues (e.g. lysylbradykinin) were inhibited in the presence of thapsigargin, whereas kinin responses were potentiated if the peptide was added following a stimulus which increases cyclic AMP. 4. From the data given here and the known behaviour of colonic epithelia it is concluded that thapsigargin increases Cai by a non-ionophoric mechanism by release from internal stores. Calcium-stimulated calcium influx then follows resulting in the opening of basolateral K channels, increasing the electrochemical gradient for chloride efflux, or alternatively by activating anion...Continue Reading

References

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Citations

Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·O ThastrupA P Dawson
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·A SchönthalJ R Feramisco
May 1, 1992·British Journal of Pharmacology·R M HendersonA W Cuthbert
Jun 1, 1993·British Journal of Pharmacology·U KachintornK E Barrett
Nov 1, 1995·British Journal of Pharmacology·C T Taylor, A W Baird
Jul 23, 2014·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Balázs RadaThomas L Leto
Oct 1, 1993·British Journal of Pharmacology
Apr 17, 2013·The Journal of Cell Biology·Edward AvezovDavid Ron
Sep 17, 2009·Immunological Reviews·Murali Prakriya
Aug 18, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mauri E KrouseJeffrey J Wine
Jul 22, 1991·Proceedings. Biological Sciences·R J PicklesA W Cuthbert
May 8, 2009·Biological & Pharmaceutical Bulletin·Agung Endro NugrohoKazutaka Maeyama
Mar 30, 2001·The Journal of Biological Chemistry·J E Keller, E A Neale
Jan 22, 1998·The American Journal of Physiology·S MoonJ J Wine
Oct 13, 2000·American Journal of Physiology. Cell Physiology·E J ThomasM I Lethem
Aug 4, 1998·The American Journal of Physiology·E R KokoskaT A Miller

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