{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T22:23:20Z","timestamp":1672611800985},"reference-count":32,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[1999,4,1]]},"abstract":"<jats:p>We have investigated the hypothesis that different contractile agonists activate distinct catalytic subunits of phosphoinositide (PI) 3-kinase in smooth muscle cells. Endothelin (10<jats:sup>\u22127<\/jats:sup>M) induced a sustained increase in PI 3-kinase activity at both 30 s and 4 min of stimulation (151.5 \u00b1 8.5% at 30 s and 175.8 \u00b1 8.7% at 4 min, P &lt; 0.005). Preincubation of smooth muscle cells with the tyrosine kinase inhibitor genistein (3 \u03bcM) resulted in a significant inhibition of both C<jats:sub>2<\/jats:sub>ceramide-induced and endothelin-induced PI 3-kinase activation and contraction. Preincubation with herbimycin A, an Src kinase inhibitor (3 \u03bcM), inhibited only C<jats:sub>2<\/jats:sub>ceramide-induced PI 3-kinase activation and contraction. Western blotting using Src kinase antibody showed that C<jats:sub>2<\/jats:sub>ceramide, not endothelin, stimulated the phosphorylation of Src kinase. Western blotting and immunoprecipitation with PI 3-kinase antibodies to the regulatory subunit p85 and the catalytic subunits p110\u03b1 and p110\u03b3 indicated that both endothelin and C<jats:sub>2<\/jats:sub>ceramide interacted with the regulatory subunit p85; endothelin interacted with the catalytic subunits p110\u03b1 and p110\u03b3, whereas C<jats:sub>2<\/jats:sub>ceramide interacted only with the catalytic subunit p110\u03b1. In summary, C<jats:sub>2<\/jats:sub>ceramide activated PI 3-kinase p110\u03b1 subunit by a tyrosine kinase-mediated pathway, whereas endothelin-induced contraction, unlike C<jats:sub>2<\/jats:sub>ceramide, was not mediated by the activation of Src kinase but was mediated by G protein activation of both p110\u03b1 and p110\u03b3 subunits (type IA and IB) of PI 3-kinase.<\/jats:p>","DOI":"10.1152\/ajpgi.1999.276.4.g853","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T09:46:14Z","timestamp":1514108774000},"page":"G853-G861","source":"Crossref","is-referenced-by-count":5,"title":["Differential activation of phosphoinositide 3-kinase by endothelin and ceramide in colonic smooth muscle cells"],"prefix":"10.1152","volume":"276","author":[{"given":"Xuehui","family":"Su","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0656"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinglang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0656"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adenike","family":"Ibitayo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0656"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalil N.","family":"Bitar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0656"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"issue":"23","key":"B1","first-page":"G537","volume":"260","author":"Bitar K. 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