{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:41:32Z","timestamp":1762864892134},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":3999,"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":[[1998,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The rat CCK<jats:sub>A<\/jats:sub> and CCK<jats:sub>B<\/jats:sub> receptors were stably expressed in Chinese hamster ovary (CHO\u201009) cells in order to compare modes of signal transduction and effects of protein kinase C (PKC) thereupon.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Spectrofluorophotometry of Fura\u20102\u2010loaded cells revealed that both receptors retained their pharmacological characteristics following expression in CHO cells. Sulphated cholecystokinin\u2010(26\u201033)\u2010peptide amide (CCK\u20108\u2010S) increased the cytosolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in CCK<jats:sub>A<\/jats:sub> cells, measured as an increase in Fura\u20102 fluorescence emission ratio, 1000 fold more potently than its non\u2010sulphated form (CCK\u20108\u2010NS) (EC<jats:sub>50<\/jats:sub> values of 0.19\u2003n<jats:sc>M<\/jats:sc> and 0.18\u2003\u03bc<jats:sc>M<\/jats:sc>, respectively). By contrast, CCK\u20108\u2010S and CCK\u20108\u2010NS were equally potent in CCK<jats:sub>B<\/jats:sub> cells (EC<jats:sub>50<\/jats:sub> values of 0.86\u2003n<jats:sc>M<\/jats:sc> and 1.18\u2003n<jats:sc>M<\/jats:sc>, respectively). The CCK<jats:sub>A<\/jats:sub> receptor agonist JMV\u2010180 increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> only in CCK<jats:sub>A<\/jats:sub> cells. Likewise, pentagastrin increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> only in CCK<jats:sub>B<\/jats:sub> cells. Finally, CCK\u20108\u2010S\u2010induced Ca<jats:sup>2+<\/jats:sup> signalling through the CCK<jats:sub>A<\/jats:sub> receptor was most potently inhibited by the CCK<jats:sub>A<\/jats:sub> receptor antagonist L364,718, whereas the CCK<jats:sub>B<\/jats:sub> receptor antagonist L365,260 was more potent in CCK<jats:sub>B<\/jats:sub> cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Receptor\u2010mediated activation of adenylyl cyclase was measured in the presence of the inhibitor of cyclic nucleotide phosphodiesterase activity, 3\u2010isobutyl\u20101\u2010methylxanthine. CCK\u20108\u2010S and, to a lesser extent, CCK\u20108\u2010NS, but not JMV\u2010180 or pentagastrin, stimulated the accumulation of cyclicAMP in CCK<jats:sub>A<\/jats:sub> cells. By contrast, none of these agonists increased cyclicAMP in CCK<jats:sub>B<\/jats:sub> cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Short\u2010term (3\u2003min) pretreatment with the PKC activator 12\u2010<jats:italic>O<\/jats:italic>\u2010tetradecanoylphorbol 13\u2010acetate (TPA) evoked a rightward shift of the dose\u2010response curve for the Ca<jats:sup>2+<\/jats:sup> mobilizing effect of CCK\u20108\u2010S in both cell lines. In addition, short\u2010term TPA pretreatment markedly reduced CCK\u20108\u2010S\u2010induced cyclicAMP accumulation in CCK<jats:sub>A<\/jats:sub> cells. In both cases, the inhibitory effect of TPA was abolished by the PKC inhibitors, GF\u2010109203X and staurosporine, whereas no inhibition was observed with the inactive phorbol ester, 4\u2010\u03b1\u2010phorbol 12\u2010myristate 13\u2010acetate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>During prolonged TPA treatment, the cells gradually recovered from phorbol ester inhibition and in the case of CCK\u20108\u2010S\u2010induced Ca<jats:sup>2+<\/jats:sup> mobilization complete recovery was achieved after 24\u2003h of TPA treatment. Western blot analysis revealed that this recovery was paralleled by down\u2010regulation of PKC\u2010\u03b1, suggesting the involvement of this PKC isotype in the inhibitory action of TPA.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study demonstrates that following expression in CHO cells (i) both CCK<jats:sub>A<\/jats:sub> and CCK<jats:sub>B<\/jats:sub> receptors are coupled to Ca<jats:sup>2+<\/jats:sup> mobilization, (ii) only CCK<jats:sub>A<\/jats:sub> receptors are coupled to cyclicAMP formation and (iii) with both receptors signalling is inhibited by PKC.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 1189\u20131197; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701713\">10.1038\/sj.bjp.0701713<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701713","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:25:05Z","timestamp":1106940305000},"page":"1189-1197","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Protein kinase C\u2010mediated inhibition of transmembrane signalling through CCK<sub>A<\/sub> and CCK<sub>B<\/sub> receptors"],"prefix":"10.1111","volume":"123","author":[{"given":"R L L.","family":"Smeets","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M A.","family":"Fouraux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S E.","family":"van Emst\u2010de Vries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J J H H M.","family":"De Pont","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P H G M.","family":"Willems","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1210561"},{"key":"e_1_2_6_3_1","first-page":"307","article-title":"Cholecystokinin increases intracellular calcium concentration in native Cho\u2010K1 cells through the activation of Cck\u2010A receptors","volume":"4","author":"Dal Forno G.","year":"1994","journal-title":"Pharmacol. Commun."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90117-1"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4179(96)90025-6"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(92)90080-F"},{"key":"e_1_2_6_7_1","first-page":"151","volume-title":"The Pancreas: Biology, Pathobiol\u2010ogy, and Disease","author":"Gardner J.D.","year":"1993"},{"key":"e_1_2_6_8_1","first-page":"G840","article-title":"Multiple kinases phosphorylate the pancreatic cholecystokinin receptor in an agonist\u2010dependent manner","volume":"264","author":"Gates L.K.","year":"1993","journal-title":"Am. J. Physiol."},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.8.3605"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81734-H"},{"key":"e_1_2_6_11_1","first-page":"G594","article-title":"A new Cck analogue differentiates two functionally distinct Cck receptors in rat and mouse pancreatic acini","volume":"257","author":"Matozaki T.","year":"1989","journal-title":"Am. J. Physiol."},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"6247","DOI":"10.1016\/S0021-9258(19)39317-2","article-title":"Two functionally distinct cholecystokinin receptors show different modes of actions on Ca2+ mobilization and phospholipid hydrolysis in isolated rat pancreatic acini","volume":"265","author":"Matozaki T.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.7.3750"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)91557-7"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18061.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(96)90045-7"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)00106-4"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)49451-9"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1523\/JNEUROSCI.04-04-01021.1984","article-title":"Cholecystokinin receptors: Biochemical demonstration and autoradiographic localization in rat brain and pancreas using [3H]\u2010cholecystokinin\u20108 as radioligand","volume":"4","author":"Van Dijk A.","year":"1984","journal-title":"J. Neurosci."},{"key":"e_1_2_6_20_1","first-page":"G628","article-title":"Cholecystokinin receptors","volume":"269","author":"Wank S.A.","year":"1995","journal-title":"Am. J. Physiol."},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.3125"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.18.8691"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(84)90163-6"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(87)90119-4"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(93)90084-J"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374609"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(95)90010-1"},{"key":"e_1_2_6_28_1","first-page":"167","volume-title":"The Pancreas: Biology, Pathobiology, and Disease","author":"Williams J.A.","year":"1993"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1993.265.5.G999"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701713","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701713","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0701713","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T01:16:19Z","timestamp":1698455779000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0701713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,3]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1998,3]]}},"alternative-id":["10.1038\/sj.bjp.0701713"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0701713","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,3]]},"assertion":[{"value":"2009-02-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}