{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T13:14:36Z","timestamp":1718111676261},"reference-count":40,"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":3438,"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":[[1999,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effects of wortmannin, an inhibitor of phosphatidylinositol (PI) kinases and myosin light chain kinase, on the quantal release of neurotransmitter from mouse phrenic nerve were investigated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Wortmannin (10\u2013100\u2003\u03bc<jats:sc>M<\/jats:sc>) initially enhanced, thereafter progressively depressed spontaneous quantal discharge (miniature endplate potential, mepp). The mean amplitude and the amplitude distribution of mepp were not altered.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The compound inhibited and prevented the intensive quantal release evoked by high KC1 solution as well as the mepp burst induced by \u03b1\u2010latrotoxin, a polypeptide toxin that possesses Ca<jats:sup>2+<\/jats:sup>\u2010independent synaptic action to trigger quantal release. The inhibitory actions of wortmannin were partially reversible.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Wortmannin depressed the amplitude of endplate potentials (epps) and increased the coefficient of variance of epps. The profile of epps in response to high frequency nerve stimulation exhibited fluctuations between run\u2010down and run\u2010up. The phenomenon is thus different from the consistency of run\u2010up characteristic as the motor nerve Ca<jats:sup>2+<\/jats:sup> channel is blocked by \u03c9\u2010agatoxin IVA.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LY294002, another inhibitor of PI 3\u2010kinase, raised mepp frequency without causing late phase suppressions. The compound did not inhibit KC1\u2010, \u03b1\u2010latrotoxin\u2010 or nerve stimulation\u2010evoked quantal release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The results suggest that wortmannin could depress quantal release beyond the step of Ca<jats:sup>2+<\/jats:sup> channel blockade, probably by interfering with the exocytotic cascade.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 142\u2013148; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702754\">10.1038\/sj.bjp.0702754<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702754","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:24:47Z","timestamp":1106943887000},"page":"142-148","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of quantal release from motor nerve by wortmannin"],"prefix":"10.1111","volume":"128","author":[{"given":"S J","family":"Hong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C C","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.18.8328"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-08-02914.1998"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0928-4257(96)80552-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.270.5.C1405"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1986.tb14594.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01366-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5255.1533"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.61.1.753"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.88.1.59"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90070-1"},{"key":"e_1_2_7_12_1","first-page":"413","volume-title":"Venom Phospholipase A2 Enzymes: Structure, Function and Mechanisms","author":"FLETCHER J.E.","year":"1997"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70192-6"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/374173a0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.57.2.315"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020517"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701898"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.21.6188"},{"key":"e_1_2_7_19_1","first-page":"329","volume-title":"Protein Kinesis: The Dynamics of Protein Trafficking and Stability","author":"JAHN R.","year":"1995"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80332-3"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-12-07695.1994"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.3.648"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)93898-8"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1973.sp010348"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.4049\/jimmunol.156.5.1942","article-title":"The phosphatidylinositol 3\u2010kinase inhibitor wortmannin blocks mast cell exocytosis but not IL\u20106 production","volume":"156","author":"MARQUARDT D.L.","year":"1996","journal-title":"J. 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