Role of phosphatidylinositol 3-kinase in acetylcholine-induced dilatation of rat basilar artery

Jiro Kitayama, Takanari Kitazono, Setsuro Ibayashi, Masanori Wakisaka, Yoshimasa Watanabe, Masahiro Kamouchi, Tetsuhiko Nagao, Masatoshi Fujishima

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Abstract

Background and Purpose - We tested the hypothesis that activation of phosphatidylinositol (PI) 3-kinase is involved in dilator responses of the basilar artery to acetylcholine in vivo. Methods - Responses of the basilar artery were measured by the cranial window technique in anesthetized rats. To examine the role of PI 3-kinase in acetylcholine-induced calcium signaling, we measured intracellular free calcium concentration ([Ca2+](i)) of cultured rat basilar arterial endothelial cells using a fluorescent calcium indicator, indo 1. Results - Topical application of acetylcholine (10-6, 10-5.5, and 10-5 mol/L) increased the diameter of the basilar artery by 8±1%, 14±2%, and 24±3%, respectively. An inhibitor of PI 3-kinase, wortmannin (10-8 mol/L), did not change the baseline diameter of the artery. In the presence of wortmannin, acetylcholine (10-6, 10-5.5, and 10-5 mol/L) dilated the artery only by 3±2%, 6±2%, and 12±2%, respectively. Thus, wortmannin attenuated acetylcholine-induced dilatation of the basilar artery (P<0.05 versus control). Wortmannin had no effect on dilatation of the artery in response to a nitric oxide donor, sodium nitroprusside. LY294002, another inhibitor of PI 3-kinase, also inhibited dilator response of the basilar artery to acetylcholine. Acetylcholine produced an increase in [Ca2+](i) of the endothelial cells. Genistein, an inhibitor of tyrosine kinase, markedly attenuated acetylcholine-induced calcium influx to the cells; however, wortmannin had no effect on acetylcholine-induced calcium changes. Conclusions - These results suggest that acetylcholine-induced dilatation of the basilar artery is mediated, at least in part, by activation of PI 3-kinase in vivo. Acetylcholine-induced [Ca2+](i) changes of the endothelial cells may not be mediated by activation of the kinase. PI 3-kinase as well as [Ca2+](i) may play an important role in the acetylcholine-induced nitric oxide production of the basilar arterial endothelial cells.

Original languageEnglish
Pages (from-to)2487-2493
Number of pages7
JournalStroke
Volume31
Issue number10
DOIs
Publication statusPublished - Jan 1 2000

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Phosphatidylinositol 3-Kinase
Basilar Artery
Acetylcholine
Dilatation
Endothelial Cells
Calcium
Arteries
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Calcium Signaling
Nitric Oxide Donors
Genistein
Nitroprusside
Protein-Tyrosine Kinases

All Science Journal Classification (ASJC) codes

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

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Role of phosphatidylinositol 3-kinase in acetylcholine-induced dilatation of rat basilar artery. / Kitayama, Jiro; Kitazono, Takanari; Ibayashi, Setsuro; Wakisaka, Masanori; Watanabe, Yoshimasa; Kamouchi, Masahiro; Nagao, Tetsuhiko; Fujishima, Masatoshi.

In: Stroke, Vol. 31, No. 10, 01.01.2000, p. 2487-2493.

Research output: Contribution to journalArticle

Kitayama, J, Kitazono, T, Ibayashi, S, Wakisaka, M, Watanabe, Y, Kamouchi, M, Nagao, T & Fujishima, M 2000, 'Role of phosphatidylinositol 3-kinase in acetylcholine-induced dilatation of rat basilar artery', Stroke, vol. 31, no. 10, pp. 2487-2493. https://doi.org/10.1161/01.STR.31.10.2487
Kitayama, Jiro ; Kitazono, Takanari ; Ibayashi, Setsuro ; Wakisaka, Masanori ; Watanabe, Yoshimasa ; Kamouchi, Masahiro ; Nagao, Tetsuhiko ; Fujishima, Masatoshi. / Role of phosphatidylinositol 3-kinase in acetylcholine-induced dilatation of rat basilar artery. In: Stroke. 2000 ; Vol. 31, No. 10. pp. 2487-2493.
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AU - Watanabe, Yoshimasa

AU - Kamouchi, Masahiro

AU - Nagao, Tetsuhiko

AU - Fujishima, Masatoshi

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N2 - Background and Purpose - We tested the hypothesis that activation of phosphatidylinositol (PI) 3-kinase is involved in dilator responses of the basilar artery to acetylcholine in vivo. Methods - Responses of the basilar artery were measured by the cranial window technique in anesthetized rats. To examine the role of PI 3-kinase in acetylcholine-induced calcium signaling, we measured intracellular free calcium concentration ([Ca2+](i)) of cultured rat basilar arterial endothelial cells using a fluorescent calcium indicator, indo 1. Results - Topical application of acetylcholine (10-6, 10-5.5, and 10-5 mol/L) increased the diameter of the basilar artery by 8±1%, 14±2%, and 24±3%, respectively. An inhibitor of PI 3-kinase, wortmannin (10-8 mol/L), did not change the baseline diameter of the artery. In the presence of wortmannin, acetylcholine (10-6, 10-5.5, and 10-5 mol/L) dilated the artery only by 3±2%, 6±2%, and 12±2%, respectively. Thus, wortmannin attenuated acetylcholine-induced dilatation of the basilar artery (P<0.05 versus control). Wortmannin had no effect on dilatation of the artery in response to a nitric oxide donor, sodium nitroprusside. LY294002, another inhibitor of PI 3-kinase, also inhibited dilator response of the basilar artery to acetylcholine. Acetylcholine produced an increase in [Ca2+](i) of the endothelial cells. Genistein, an inhibitor of tyrosine kinase, markedly attenuated acetylcholine-induced calcium influx to the cells; however, wortmannin had no effect on acetylcholine-induced calcium changes. Conclusions - These results suggest that acetylcholine-induced dilatation of the basilar artery is mediated, at least in part, by activation of PI 3-kinase in vivo. Acetylcholine-induced [Ca2+](i) changes of the endothelial cells may not be mediated by activation of the kinase. PI 3-kinase as well as [Ca2+](i) may play an important role in the acetylcholine-induced nitric oxide production of the basilar arterial endothelial cells.

AB - Background and Purpose - We tested the hypothesis that activation of phosphatidylinositol (PI) 3-kinase is involved in dilator responses of the basilar artery to acetylcholine in vivo. Methods - Responses of the basilar artery were measured by the cranial window technique in anesthetized rats. To examine the role of PI 3-kinase in acetylcholine-induced calcium signaling, we measured intracellular free calcium concentration ([Ca2+](i)) of cultured rat basilar arterial endothelial cells using a fluorescent calcium indicator, indo 1. Results - Topical application of acetylcholine (10-6, 10-5.5, and 10-5 mol/L) increased the diameter of the basilar artery by 8±1%, 14±2%, and 24±3%, respectively. An inhibitor of PI 3-kinase, wortmannin (10-8 mol/L), did not change the baseline diameter of the artery. In the presence of wortmannin, acetylcholine (10-6, 10-5.5, and 10-5 mol/L) dilated the artery only by 3±2%, 6±2%, and 12±2%, respectively. Thus, wortmannin attenuated acetylcholine-induced dilatation of the basilar artery (P<0.05 versus control). Wortmannin had no effect on dilatation of the artery in response to a nitric oxide donor, sodium nitroprusside. LY294002, another inhibitor of PI 3-kinase, also inhibited dilator response of the basilar artery to acetylcholine. Acetylcholine produced an increase in [Ca2+](i) of the endothelial cells. Genistein, an inhibitor of tyrosine kinase, markedly attenuated acetylcholine-induced calcium influx to the cells; however, wortmannin had no effect on acetylcholine-induced calcium changes. Conclusions - These results suggest that acetylcholine-induced dilatation of the basilar artery is mediated, at least in part, by activation of PI 3-kinase in vivo. Acetylcholine-induced [Ca2+](i) changes of the endothelial cells may not be mediated by activation of the kinase. PI 3-kinase as well as [Ca2+](i) may play an important role in the acetylcholine-induced nitric oxide production of the basilar arterial endothelial cells.

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