Central cardiovascular regulation of tachykinin peptides : The autonomic nervous system and endocrine system

速激肽的中枢心血管调节：自主神经系统和内分泌系统

• 批准号: 02671059
• 负责人: TAKANO Yukio
• 金额: $ 1.34万
• 依托单位: Fukuoaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02671059/
• 关键词: Blood pressure; substance P; tachykinin peptides; endothelial cell; vasopressin; hypothalamus; 高血圧; バゾプレッシン; ペプチド; 血管

1. Central Cardiovascular Regulation of Tachykinin PeptidesThe central pressor responses to the tachykinin peptides were dose-dependent, reaching maxima 4-6 min after injections of the peptides and then persisting for at least 40 min. The pressor responses due to substance P (SP), neurokinin A (NKA) and neuropeptide gamma (NPgamma) were blocked by sympathetic blocking agents. In contrast, the pressor response to an neurokinin B (NKB) analogue senktide was not blocked by the ganglionic blocking agent or adrenalectomy. The senktide-induced pressor response was inhibited by pretreatment with a vasopressin antagonist, and senktide caused an increase in plasma vasopressin level. However, the vasopressin antagonist did not influence the SP-, NKA- and NPgamma-induced pressor responses.These results suggest that central SP, NKA and NPgamma, derived from the preprotachykinin A gene, increase the blood pressure (BP) and heart rate via sympathetic nerve activity, whereas central NKB, derived from … More the preprotachykinin B gene, increase the BP via release of vasopressin from the hypothalamus2. Pharmacological properties of the tachykinin receptor subtype in the endothelial cell and vasodilation.Vascular endothelial cells are involved in the regulation of vascular tone through production of an endothelium-derived relaxing factor (EDRF). SP and related peptides have shown to cause endotheliumdependent relaxation of precontracted arteries of several mammalian species. Agonists for the NK-1 tachykinin receptor elicited the potent, transient and endothelium-dependent relaxation. SP-induced relaxation and increase of cGMP content were inhibited by hemoglobin, methylene blue, L-NG-monomethyl-D-arginine. These results suggest that the relaxation induced by SP is mediated by EDRF.In addition, we examined ^<125>I-Bolton-Hunter SP binding to the endothelial cell membranes of porcine aorta. The cells had a single high affinity binding site with Kd = 0.10 nM and Bmax = 52.2 fmol/mg protein. GTP analog caused a marked reduction in the number of the binding sites. NK-1 receptor agonists were most potent for displacing of ^<125>I-BHSP binding. This result is in agreement with the results of the vasodilating responses. Less

1.速激肽的中枢心血管调节速激肽的中枢升压反应是剂量依赖性的，注射肽后4-6分钟达到最大值，然后持续至少40分钟。 P 物质 (SP)、神经激肽 A (NKA) 和神经肽 γ (NPgamma) 引起的升压反应被交感神经阻断剂阻断。相比之下，神经激肽 B (NKB) 类似物 Senktide 的升压反应不会被神经节阻断剂或肾上腺切除术阻断。用加压素拮抗剂预处理可抑制森肽诱导的升压反应，并且森肽引起血浆加压素水平升高。然而，加压素拮抗剂并不影响 SP、NKA 和 NPgamma 诱导的升压反应。这些结果表明，源自前原速激肽 A 基因的中枢 SP、NKA 和 NPgamma 通过交感神经活动增加血压 (BP) 和心率，而源自前原速激肽 B 基因的中枢 NKB 则通过交感神经活动增加血压 (BP) 和心率。 下丘脑释放加压素2。内皮细胞中速激肽受体亚型的药理学特性和血管舒张作用。血管内皮细胞通过产生内皮源性舒张因子 (EDRF) 参与血管张力的调节。 SP 和相关肽已显示可引起几种哺乳动物预收缩动脉的内皮依赖性松弛。 NK-1 速激肽受体激动剂可引发有效的、短暂的、内皮依赖性的松弛。 SP诱导的松弛和cGMP含量的增加被血红蛋白、亚甲蓝、L-NG-单甲基-D-精氨酸抑制。这些结果表明SP诱导的舒张是由EDRF介导的。此外，我们检测了125 I-Bolton-Hunter SP与猪主动脉内皮细胞膜的结合。这些细胞具有单个高亲和力结合位点，Kd = 0.10 nM，Bmax = 52.2 fmol/mg 蛋白质。 GTP 类似物导致结合位点数量显着减少。 NK-1受体激动剂对于取代125 I-BHSP结合是最有效的。该结果与血管舒张反应的结果一致。较少的

项目成果

Saito,R.: "Characterization of tachykinin receptors in endothelial cells of porcine artery." Neuroscience Lett.,. 110. 337-342 (1990)

Saito,R.：“猪动脉内皮细胞中速激肽受体的表征。”

Saito, R., Konishi, H., Nonaka, S., Takano, Y., Shimohigashi, Y. and Kamiya, H.: "Pharmacological properties of the tachykinin receptor subtype in the endotherial cell and vasodilation." Annals. New Acad. Sci., New York. 632. 457-459 (1991)

Saito, R.、Konishi, H.、Nonaka, S.、Takano, Y.、Shimohigashi, Y. 和 Kamiya, H.：“内皮细胞中速激肽受体亚型的药理学特性和血管舒张作用。”

Takano,Y.: "Tachykinin receptor subtypes:Cardiovascular roles of tachykinin petides." Asia Pacific J.Pharmacol.6. 341-348 (1991)

Takano,Y.：“速激肽受体亚型：速激肽肽的心血管作用。”

Takano, Y. and Kamiya, H.: "Tachykinin receptor subtypes: Cardiovascular roles of tachykinin peptides." Asia Pacific J. Pharmacol.6. 341-348 (1991)

Takano, Y. 和 Kamiya, H.：“速激肽受体亚型：速激肽肽的心血管作用。”

神谷 大雄: "タキキニン受容体の細分化" 医学のあゆみ. 152. 152-152 (1990)

Daio Kamiya：“速激肽受体的细分”医学史 152. 152-152 (1990)。