{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:07:40Z","timestamp":1777910860039,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,1,2]],"date-time":"2013-01-02T00:00:00Z","timestamp":1357084800000},"content-version":"vor","delay-in-days":2407,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the present study we investigated the role of Ca<jats:sup>2+<\/jats:sup> in tetramethylpyrazine (TMP)\u2010induced anion secretion in the human colonic epithelial cell line, Caco\u20102, using the short\u2010circuit current (<jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub>) technique in conjunction with intracellular Ca<jats:sup>2+<\/jats:sup> measurements. The results showed that TMP\u2010induced <jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub> response was significantly reduced by 58.8% and 38.3% after inhibiting Ca<jats:sup>2+<\/jats:sup> ATPase of endoplasmic reticulum (ER) with thapsigargin and mobilizing ER stored Ca<jats:sup>2+<\/jats:sup> release with ATP, respectively. Conversely, thapsigargin\u2010 and ATP\u2010evoked <jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub> responses were also significantly reduced by pretreatment with TMP by 43.2% and 38.5%, respectively. Conversely, removal of extracellular Ca<jats:sup>2+<\/jats:sup>, apical but not basolateral, or the presence of the Ca<jats:sup>2+<\/jats:sup> chelator (EGTA) significantly increased TMP\u2010induced <jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub> by 47.1% and 37.8%, respectively. Similar to TMP, thapsigargin\u2010induced current increase was also enhanced by chelating extracellular Ca<jats:sup>2+<\/jats:sup> or in Ca<jats:sup>2+<\/jats:sup> free solution; however, removal of extracellular Ca<jats:sup>2+<\/jats:sup> did not significantly affect 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX)\u2010 and forskolin\u2010induced transepithelial current. Measurement of the intracellular concentration of free Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) with fura\u20102\/AM showed that TMP could induce an increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> but pretreatment with TMP significantly reduced thapsigargin\u2010evoked, but not ATP\u2010induced, [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase. These results suggest that the effect of TMP on colonic anion secretion is partly mediated by TMP\u2010increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> by acting on a target similar to thapsigargin. The observed inhibitory effect of extracellular Ca<jats:sup>2+<\/jats:sup> on Ca<jats:sup>2+<\/jats:sup>\u2010dependent anion secretion represents a novel mechanism by which Ca<jats:sup>2+<\/jats:sup>\u2010dependent regulation of epithelial electrolyte transport may be fine\u2010tuned by extracellular Ca<jats:sup>2+<\/jats:sup> in the apical domain.<\/jats:p>","DOI":"10.1016\/j.cellbi.2006.03.003","type":"journal-article","created":{"date-parts":[[2006,3,24]],"date-time":"2006-03-24T12:40:16Z","timestamp":1143204016000},"page":"547-552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Involvement of intracellular and extracellular Ca<sup>2+<\/sup> in tetramethylpyrazine\u2010induced colonic anion 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