{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:37:41Z","timestamp":1772815061855,"version":"3.50.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:p><jats:italic>Background and Purpose<\/jats:italic>\u2014Endothelin-1 (ET-1) is suggested to be a major cause of cerebral vasospasm after subarachnoid hemorrhage. However, the mechanism of ET-1\u2013induced contraction in cerebral arteries remains unclear. This study was undertaken to demonstrate the possible role of protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC) in ET-1\u2013induced contraction.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>\u2014PD-98059, damnacanthal, wortmannin, AG-490, genistein, calphostin C, and staurosporine were used to inhibit, or relax, the ET-1\u2013induced contraction of basilar artery, studied with an isometric tension system. Immunoprecipitation of MAPK in ET-1\u2013stimultated rings of basilar artery without or with the above inhibitors was studied with Western blot.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>\u2014(1) ET-1 produced concentration-dependent contraction and MAPK immunoprecipitation in rabbit basilar artery by activation of ET<jats:sub>A<\/jats:sub>but not ET<jats:sub>B<\/jats:sub>receptors. (2) MAPK inhibitors PD-98059 and U-0126 produced dose-dependent inhibition of ET-1\u2013induced contraction. (3) The Src tyrosine kinase inhibitor damnacanthal, the phosphatidylinositol-3 kinase inhibitor wortmannin, and the Janus tyrosine kinase<jats:sub>2<\/jats:sub>inhibitor AG-490 abolished ET-1\u2013induced contraction. (4) The PKC inhibitor staurosporine but not calphostin C abolished ET-1\u2013induced contraction, and the PTK inhibitor genistein partially reduced ET-1\u2013induced contraction. (5) In arteries precontracted by ET-1, PD-98059, U-0126, wortmannin, AG-490, genistein, and staurosporine produced concentration-dependent relaxation. (6) ET-1 induced a biphasic and time-dependent MAPK immunoprecipitation. (7) PD-98059, U-0126, genistein, AG-490, and damnacanthal, but not staurosporine or wortmannin, abolished the effect of ET-1 on MAPK immunoreactivity.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014This study demonstrated that MAPK may be involved in ET-1\u2013induced contraction in rabbit basilar artery. MAPK is downstream of PTK, Src, and Janus tyrosine kinase pathways but may not be downstream of phosphatidylinositol-3 kinase pathways. The possible involvement of PKC in ET-1\u2013induced contraction requires further investigation. Inhibition of these pathways may offer alternative treatment for ET-1\u2013induced contraction and cerebral vasospasm.<\/jats:p>","DOI":"10.1161\/01.str.31.2.526","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:08:03Z","timestamp":1308341283000},"page":"526-533","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["Mechanism of Endothelin-1\u2013Induced Contraction in Rabbit Basilar Artery"],"prefix":"10.1161","volume":"31","author":[{"given":"Alexander Y.","family":"Zubkov","sequence":"first","affiliation":[{"name":"From the Department of Neurosurgery, University of Mississippi Medical Center, Jackson."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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