{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T22:57:50Z","timestamp":1765666670000},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3681,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Short\u2010circuit current (<jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub>) responses to carbachol (CCh) were investigated in Colony 1 epithelia, a subpopulation of the HCA\u20107 adenocarcinoma cell line. In Krebs\u2010Henseleit (KH) buffer, CCh responses consisted of three <jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub> components: an unusual rapid decrease (the 10\u2003s spike) followed by an upward spike at 30\u2003s and a slower transient increase (the 2\u2003min peak). This response was not potentiated by forskolin; rather, CCh inhibited cyclic AMP\u2010stimulated <jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> free buffer, the decrease in forskolin\u2010elevated <jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub> after CCh was reduced, although the interactions between CCh and forskolin remained at best additive rather than synergistic. When Cl<jats:sup>\u2212<\/jats:sup> anions were replaced by gluconate, both Ca<jats:sup>2+<\/jats:sup>\u2010 and cyclic AMP\u2010mediated electrogenic responses were significantly inhibited.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Basolateral Ba<jats:sup>2+<\/jats:sup> (1\u201310\u2003m<jats:sc>M<\/jats:sc>) and 293B (10\u2003\u03bc<jats:sc>M<\/jats:sc>) selectively inhibited forskolin stimulation of <jats:italic>I<\/jats:italic><jats:sub>SC<\/jats:sub>, without altering the effects of CCh. Under Ba<jats:sup>2+<\/jats:sup>\u2010 or 293B\u2010treated conditions, CCh responses were potentiated by pretreatment with forskolin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Basolateral charybdotoxin (50\u2003n<jats:sc>M<\/jats:sc>) significantly increased the size of the 10\u2003s spike of CCh responses in both KH and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> free medium, without affecting the 2\u2003min peak. The enhanced 10\u2003s spike was inhibited by prior addition of 5\u2003m<jats:sc>M<\/jats:sc> apical Ba<jats:sup>2+<\/jats:sup>. Charybdotoxin did not affect forskolin responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In epithelial layers prestimulated with forskolin, the muscarinic antagonists atropine and 4\u2010diphenylacetoxy\u2010N\u2010methylpiperidine methiodide (4\u2010DAMP, both at 100\u2003n<jats:sc>M<\/jats:sc>) abolished subsequent 10\u2003\u03bc<jats:sc>M<\/jats:sc> CCh responses. Following addition of <jats:italic>p<\/jats:italic>\u2010fluoro hexahydro\u2010sila\u2010difenidol (<jats:italic>p<\/jats:italic>F\u2010HHSiD, 10\u2003\u03bc<jats:sc>M<\/jats:sc>) or pirenzepine (1\u2003\u03bc<jats:sc>M<\/jats:sc>), qualitative changes in the CCh response time\u2010profile also indicated a rightward shift of the agonist concentration\u2010response curve; however, 1\u2003\u03bc<jats:sc>M<\/jats:sc> gallamine had no effect. These results suggest that a single M<jats:sub>3<\/jats:sub>\u2010like receptor subtype mediates the secretory response to CCh.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is concluded that CCh and forskolin activate discrete populations of basolateral K<jats:sup>+<\/jats:sup> channels gated by either Ca<jats:sup>2+<\/jats:sup> or cyclic AMP, but that the Cl<jats:sup>\u2212<\/jats:sup> permeability of the apical membrane may limit their combined effects on electrogenic Cl<jats:sup>\u2212<\/jats:sup> secretion. In addition, CCh activates a Ba<jats:sup>2+<\/jats:sup>\u2010sensitive apical K<jats:sup>+<\/jats:sup> conductance leading to electrogenic K<jats:sup>+<\/jats:sup> transport. Both agents may also modulate HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion through a mechanism at least partially dependent on carbonic anhydrase.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 269\u2013279; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702270\">10.1038\/sj.bjp.0702270<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702270","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:54:15Z","timestamp":1106942055000},"page":"269-279","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Modulation of chloride, potassium and bicarbonate transport by muscarinic receptors in a human adenocarcinoma cell line"],"prefix":"10.1111","volume":"126","author":[{"given":"Nicholas D","family":"Holliday","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen M","family":"Cox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00233281"},{"key":"e_1_2_6_3_1","first-page":"2133","volume-title":"Physiology of the Gastrointestinal Tract","author":"BINDER H.J.","year":"1994"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050229"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(88)90002-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(96)01016-4"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.537bm.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1996.sp003954"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90138-G"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90139-H"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1987.tb11243.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.265.5.C1271"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.1.C138"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"C1224","DOI":"10.1152\/ajpcell.1989.256.6.C1224","article-title":"Multiple calcium\u2010mediated effector mechanisms regulate chloride secretory responses in T84 cells","volume":"256","author":"DHARMSATHAPHORN K.","year":"1989","journal-title":"Am. 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