Role of tyrosine kinase in serotonin-induced constriction of the basilar artery in vivo

Takanari Kitazono, Setsuro Ibayashi, Tetsuhiko Nagao, Tomoko Kagiyama, Jiro Kitayama, Masatoshi Fujishima

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20 Citations (Scopus)

Abstract

Background and Purpose - Serotonin is one of the most potent constrictors of cerebral blood vessels and is implicated in several pathological conditions, including migraine and cerebral ischemia. Recent evidence has suggested that tyrosine kinase is involved in vasocontractile responses. The objective of this study was to test the hypothesis that activation of tyrosine kinase contributes to serotonin-induced constriction of the basilar artery in vivo. Methods - Using a cranial window in anesthetized Sprague-Dawley rats, we examined effects of inhibitors of tyrosine kinase and tyrosine phosphatase on constrictor responses of the basilar artery to serotonin in vivo. Results - Serotonin (10-8, 10-7, and 10-6 mol/L) produced constriction of the basilar artery by 12 ± 2%, 27 ± 2%, and 37 ± 3%, respectively. Genistein (3x10-6 mol/L), an inhibitor of tyrosine kinase, did not affect baseline diameter of the basilar artery but attenuated serotonin-induced vasoconstriction (P<.05 versus control responses). Daidzein, an inactive analogue of genistein, did not affect serotonin-induced constriction of the basilar artery. Tyrphostin 47 (10-5 mol/L), another inhibitor of tyrosine kinase, also attenuated serotonin- induced vasoconstriction, and tyrphostin 63, an inactive analogue of tyrphostin 47, did not affect the vasoconstriction. Sodium orthovanadate (10-5 mol/L), an inhibitor of tyrosine phosphatase, enhanced serotonin- induced vasoconstriction. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C, also caused constriction of the basilar artery, which was not affected by genistein or sodium orthovanadate. Conclusions - These results suggest that serotonin-induced constriction of the basilar artery is mediated, at least in part, by activation of tyrosine kinase in vivo.

Original languageEnglish
Pages (from-to)494-498
Number of pages5
JournalStroke
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 1998

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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