{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T08:35:39Z","timestamp":1775205339841,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1993,8,1]],"date-time":"1993-08-01T00:00:00Z","timestamp":744163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1993,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Phospholipid\/calcium-dependent protein kinase (protein kinase C [PKC]) is a critical system in signal transduction of many different cells including airway smooth muscle (ASM) cells. We have previously shown that after administration of different phorbol esters, specific activators of PKC, characteristic electrical and contractile changes of ASM cells can be demonstrated. Similarly, our data showed that stimulation of PKC is implicated in the process of sensitization and the specific antigen challenge response of ASM cells. In this study we examined the effect of staurosporine, a microbial alkaloid, which has been reported to be a specific inhibitor of PKC, on sensitization- and specific antigen challenge-induced electrical and contractile changes of ASM cells. The effect of staurosporine was compared with those of amiloride, furosemide, and compounds NA-0345 and H-7, both synthetic PKC inhibitors. We used ASM preparations isolated from adult male guinea pigs (Camm-Hartley strain). Changes in both membrane potential (Em), measured by a glass microelectrode technique, and isometric force, measured by copper-beryllium strain gauge, were continuously monitored. Experiments were conducted with optimal length (Lmax) of ASM preparations and at 37\u00b0 C. We found that the exposure of ASM preparations to staurosporine, NA-0345, H-7, amiloride, and furosemide (all in 10\u221212 to 10\u22124 M) had no measurable effect on the resting membrane potential or isometric force of ASM preparations. In contrast, pretreatment of ASM preparations with staurosporine, NA-0345, H-7, amiloride, or furosemide significantly attenuated (p &amp;lt; 0.001) phorbol myristate acetate-induced changes of ASM preparations. The inhibitory effect of staurosporine, furosemide, amiloride, H-7, and NA-0345 was dose-dependent, \u2212logED50 being 9.14 \u00b1 0.13, 8.13 \u00b1 0.09, 7.59 \u00b1 0.01, 6.74 \u00b1 0.02, and 5.92 \u00b1 0.02, respectively. Pretreatment of ASM preparations with staurosporine (10\u22128 M) significantly attenuated sensitization- and specific antigen challenge-induced changes in membrane potential and isometric force. These data show that inhibition of PKC of ASM significantly interferes with sensitization- and specific antigen challenge-induced changes of ASM preparations.<\/jats:p>","DOI":"10.1164\/ajrccm\/148.2.425","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T17:46:01Z","timestamp":1365097561000},"page":"425-430","source":"Crossref","is-referenced-by-count":10,"title":["Inhibitory Effect of Staurosporine on Protein Kinase C Stimulation of Airway Smooth Muscle Cells"],"prefix":"10.1093","volume":"148","author":[{"given":"M.","family":"Souhrada","sequence":"first","affiliation":[{"name":"John B. Pierce Laboratory and Yale School of Medicine, New Haven, Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. F.","family":"Souhrada","sequence":"additional","affiliation":[{"name":"John B. 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