Specific role of tyrosine kinase in the vascular contraction produced by stretch.

酪氨酸激酶的特异作用是使血管收缩而产生牵拉。

• 批准号: 07672370
• 负责人: NAKAYAMA Koichi
• 金额: $ 1.41万
• 依托单位: Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672370/
• 关键词: mechano-reception; stretch; myogenic contraction; vascular tissue; tyrosine kinase; protein tyrosyl phosphorylation; adhesion molecule; cellar signal transduction; tyrosine kinase; cerebral artery; myogenic tone; tyrosine kinase inhbitor; geni

In order to determine whether protein tyrosine kinase mechanisms are involved in pressure-induced contraction, we compared effects of three structurally-unrelated tyrosine kinase inhibitors and orthovanadate, a tyrosine phosphatase inhibitor, on the pressure-induced contraction of the posterior cerebral artery isolated from rats. The change in vessel diameter was continuously measured with a width analyzer. Herbimycin A inhibited the pressure-induced contraction, while it only slightly inhibited contractions produced by potassium chloride or 9,11 dideoxy-11alpha, 9alpha-epoxymethano prostaglandin F2alpha (U46619). Genistein inhibited not only the pressure-induced contraction but also the U46619-induced one. Tyrphostin 23 significantly attenuated contractions in response to three different stimuli, i.e., pressure, potassium chloride, and U46619. Orthovanadate potentiated the pressure-induced contraction. These results suggest that herbimycin A is the most specific and potent inhibitor of the pressure-induced contraction and that a protein tyrosine kinase machanism may play an important role in the genesis of the pressure-induced contraction of the rat cerebral artery.

为了确定蛋白酪氨酸激酶机制是否参与了压力收缩，我们比较了三种结构无关的酪氨酸激酶抑制剂和酪氨酸磷酸酶抑制剂原钒酸对大鼠大脑后动脉压力收缩的影响。用宽度分析仪连续测量血管直径的变化。除草剂A可抑制压力引起的收缩，但对氯化钾或9，11二脱氧-11α，9α-环氧甲基前列腺素F2α(U46619)引起的收缩仅有轻微抑制作用。金雀异黄素不仅能抑制压力引起的收缩，而且还能抑制U46619引起的收缩。Tyrphostin 23显著减弱对三种不同刺激的收缩，即压力、氯化钾和U46619。原钒酸可增强压力引起的收缩。这些结果表明，去甲氧西林A是最特异和最有效的压力收缩抑制剂，蛋白酪氨酸激酶机制可能在大鼠大脑动脉压力收缩的发生中起重要作用。

项目成果

Koichi Nakayama, Tohru Nakazawa, Yoshihisa Fukuta and Yoshio Tanaka: "Stereo-selective calcium antagonistic and binding properties of the enantiomers of lemildipine in vascular tissue of pigs and dogs." Arzneim.Forsch./Drug Res.46 (II). 1045-1053 (1996)

Koichi Nakayama、Tohru Nakazawa、Yoshihisa Fukuta 和 Yoshio Tanaka：“雷米地平对映体在猪和狗血管组织中的立体选择性钙拮抗和结合特性。”

Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama.: "Biol. Pharmacol. Bull." Flow regulates vasodilator responses to acetylcholine in the isolated canine mesenteric arterial bed., ((in press.))

Tsutomu Nakahara、Kunio Ishii、Yoshio Tanaka 和 Koichi Nakayama：“Biol. Pharmacol. Bull。”

Tsutomu Nakahara,Kunio Ishii,Yoshio Tanaka and Koichi Nakayama.: "Involvement of neurohumoral factors in the pressor mechanism of N^G-nitro-L-arginine." Eur.J.Pharmacol.287. 49-56 (1995)

Tsutomu Nakahara、Kunio Ishii、Yoshio Tanaka 和 Koichi Nakayama.：“神经体液因子参与 N^G-硝基-L-精氨酸的升压机制。”

Tsutomu Nakahara, Kunio Ishii, Yoshio Tanaka and Koichi Nakayama: "Involvement of neurohumoral factors in the pressor mechanism of N^G-nitro-L-arginine" Eur.J.Pharmacol.287. 49-56 (1995)

Tsutomu Nakahara、Kunio Ishii、Yoshio Tanaka 和 Koichi Nakayama：“N^G-硝基-L-精氨酸升压机制中神经体液因子的参与”Eur.J.Pharmacol.287。

Naohiro Masumoto, Koichi Nakayama, Akihiro Oyabe, Mayumi Uchino, Kunio Ishii, Kazuo Obara and Yoshiyuki Tanabe: "Specific attenuation of the pressure-induced contraction of rat cerebral artery by herbimycin A." Eur.J.Pharmacol.(in press).

Naohiro Masumoto、Koichi Nakayama、Akihiro Oyabe、Mayumi Uchino、Kunio Ishii、Kazuo Obara 和 Yoshiyuki Tanabe：“除草霉素 A 对压力引起的大鼠脑动脉收缩的特异性减弱。”