{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T14:13:05Z","timestamp":1697983985446},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":5970,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1988,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The influence of isoquinolinesulfonamides (H\u20107 and H\u20108), phenothiazines(trifluoperazine and fluphenazine), and a naphthalenesulfonamide (N\u2010(6\u2010aminohexyl)\u20105\u2010chloro\u20101\u2010naphthalenesulfonamide (W\u20107)) on stimulated superoxide anion production and phosphatidyl inositol (PI) cycle activity was investigated in the guinea pig alveolar macrophage. All five drugs were able to inhibit superoxide anion production stimulated by n\u2010formyl\u2010nel\u2010leu\u2010phe (FNLP), leukotriene B<jats:sub>4<\/jats:sub> (LTB<jats:sub>4<\/jats:sub>), and phorbol\u201012,13\u2010dibutyrate (PDB). The order of potency was trifluoperazine \u2265 fluphenzine &gt; H\u20107 = W\u20107 &gt; H\u20108. The dose response curves could be shifted to less efficacy by increasing extracellular calcium. By itself, W\u20107 markedly stimulated 45Ca<jats:sup>+2<\/jats:sup> efflux, efflux, fluphenazine and trifluoperazine slightly stimulated 45Ca<jats:sup>+2<\/jats:sup> efflux from macrophages preloaded with 45Ca<jats:sup>+2<\/jats:sup>. Consistent with these results, W\u20107 markedly stimulated PI cycle activity, fluphenazine and trifluoperazine slightly stimulated PI cycle activity, while H\u20107 and H\u20108 had no significant effects on PI cycle activity. In addition, W\u20107 by itself was able to stimulate a weak and short\u2010lived \u201cburst\u201d of superoxide anion production. In order to evaluate whether a site of action of the inhibitors was at protein kinase C and whether protein kinase C was involved in terminating the normally short\u2010lived FNLP\u2010 and LTB<jats:sub>4<\/jats:sub>\u2010stimulated macrophage activation, fluphenazine and H\u20107 were used to evaluate the duration of FNLP\u2010 and LTB<jats:sub>4<\/jats:sub>\u2010stimulated PI cycle activity, at concentrations of the inhibitors that significantly blocked stimulated superoxide anion production. In all cases, FNLP and LTB<jats:sub>4<\/jats:sub> still stimulated PI cycle activity, which still terminated even though protein kinase C was inhibited. These results suggest that all five drugs block protein kinase C, but H\u20107 was the most specific in its action at protein kinase C, while the phenothiazines and W\u20107 have multiple sites of action. In addition, these results suggest that protein kinase C may not function to cause the termination of FNLP\u2010 and LTB<jats:sub>4<\/jats:sub>\u2010stimulated PI cycle activity and subsequent superoxide anion production.<\/jats:p>","DOI":"10.1002\/jcp.1041370106","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T10:55:56Z","timestamp":1109415356000},"page":"45-54","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of macrophage activation by isoquinolinesulfonamides, phenothiazines, and a napthalenesulfonamide"],"prefix":"10.1002","volume":"137","author":[{"given":"Andrij","family":"Holian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark K.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanh V.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoltan J.","family":"Devenyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(81)90020-9"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)90203-1"},{"key":"e_1_2_1_5_1","first-page":"673","article-title":"Chemotactic activity of guinea pig alveolar macrophages","volume":"117","author":"Dauber J. 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