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

1.速激肽的中枢心血管调节速激肽的中枢升压反应呈剂量依赖性，在注射后4-6分钟达到最大值，并持续至少40分钟。交感神经阻滞剂可阻断P物质(SP)、神经激肽A(NKA)和神经肽γ(NPGamma)引起的升压反应。相反，神经节阻滞剂或肾上腺切除术不能阻断神经激肽B(NKB)类似物的升压反应。升压素拮抗剂可抑制升压素引起的升压反应，升压素可使血浆升压素水平升高。这些结果表明，来源于前速激肽A基因的中枢SP、NKA和NPGamma通过交感神经活动来增加血压和心率，而来源于…的中枢NkB更多的原速激肽B基因，通过从下丘脑释放加压素来增加血压。血管内皮细胞中速激肽受体亚型的药理学特性和血管扩张。血管内皮细胞通过产生内皮衍生的松弛因子(EDRF)参与调节血管张力。已有研究表明，SP及其相关多肽可引起几种哺乳动物预先收缩的动脉内皮依赖性松弛。NK-1Tachykinin受体激动剂可引起强烈的、短暂的和内皮依赖性的松弛。血红蛋白、亚甲蓝、L-NG-单甲基-D-精氨酸均能抑制SP引起的松弛和cGMP含量的增加。这些结果表明，SP的松弛作用是由EDRF介导的。此外，我们还检测了~(125)&gt；i-Bolton-Hunter SP与猪主动脉内皮细胞膜的结合。细胞具有单一的高亲和力结合部位，Kd=0.10 nM，Bmax=52.2fmol/mg蛋白。GTP类似物显著减少了结合位点数。NK-1受体激动剂最能取代~(125)&gt；I-BHSP结合。这一结果与血管扩张反应的结果是一致的。较少

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