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首页> 外文期刊>Life sciences >Transglutaminase-synthesized spermine derivative of substance P recognizes rat portal vein neurokinin-3 receptors.
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Transglutaminase-synthesized spermine derivative of substance P recognizes rat portal vein neurokinin-3 receptors.

机译：转谷氨酰胺酶合成的P物质精胺衍生物可识别大鼠门静脉神经激肽3受体。

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The effects of the transglutaminase-synthesized polyamine derivatives of Substance P (SP) have been further characterized by their ability to contract in vitro the rat portal vein strip (RPV), a pharmacological preparation particularly rich in NK-3 receptors. The effects of selective agonists of NK-1, NK-2 and NK-3 receptors [Sar9,Met(O(2))11]SP, beta-Ala8 NKA(4-10), and senktide respectively, were also evaluated by measuring RPV concentration-response curves. Peptide [GR-82334 (NK-1) and MEN-10,376 (NK-2)] and nonpeptide [WIN 51,708 (NK-1) and SR 142801 (NK-3)] NK receptor antagonists were used to confirm the participation of the different NK receptors to contractile response. Our results demonstrated that the spermine derivative of SP (Spm-SP), previously shown to be unable to recognize NK-1 and NK-2 receptors in some bioassays, contracts RPV (EC50 = 588 nM) better than the native neuropeptide (EC50 = 1120 nM). A pretreatment with thiorphan, an inhibitor of neutral endopeptidases, significantly reduced such a difference. While this inhibitor shifts the SP concentration-response curves to the left (EC50 = 720 nM) the action of Spm-SP and [Sar9,Met(O(2))11]SP were completely thiorphan-resistant. In the absence of thiorphan we found the following rank order of potency: senktide > > beta-Ala8 NKA(4-10) > [Sar9,Met(O(2))11]SP = Spm-SP > SP. Among the mentioned NK receptor antagonists, only the selective NK-3 receptor antagonist, SR 142801, shifted to the right Spm-SP and [Sar9,Met(O(2))11]SP concentration-response curve, showing pKB values of 5.84 and 5.88, respectively. Therefore, the reported results suggest that the introduction of a Spm moiety into the SP alters the parent peptide molecule by increasing its affinity for NK-3 receptors and/or by preventing its degradation by some proteolytic enzymes.
机译：转谷氨酰胺酶合成的P物质（SP）的多胺衍生物的作用进一步被表征为具有体外收缩大鼠门静脉条（RPV）的能力，大鼠门静脉条是一种特别富含NK-3受体的药理制剂。还分别通过以下方法评估了NK-1，NK-2和NK-3受体[Sar9，Met（O（2））11] SP，β-Ala8NKA（4-10）和senktide选择性激动剂的作用。测量RPV浓度-响应曲线。肽[GR-82334（NK-1）和MEN-10,376（NK-2）]和非肽[WIN 51,708（NK-1）和SR 142801（NK-3）] NK受体拮抗剂被用于确认是否参与了不同的NK受体对收缩反应。我们的研究结果表明，SP的精胺衍生物（Spm-SP）先前在某些生物测定中无法识别NK-1和NK-2受体，其RPV（EC50 = 588 nM）优于天然神经肽（EC50 = 1120 nM）。用中性内肽酶的抑制剂硫氢芬进行的预处理显着降低了这种差异。虽然此抑制剂将SP浓度-响应曲线向左移动（EC50 = 720 nM），但Spm-SP和[Sar9，Met（O（2））11] SP的作用是完全对硫柳烷具有抗性的。在没有噻虫啉的情况下，我们发现效价的等级顺序如下：senktide beta-Ala8 NKA（4-10）> [Sar9，Met（O（2））11] SP = Spm-SP> SP。在上述NK受体拮抗剂中，只有选择性NK-3受体拮抗剂SR 142801移至右侧的Spm-SP和[Sar9，Met（O（2（））11]] SP浓度-响应曲线，显示pKB值为5.84和5.88。因此，报道的结果表明，通过增加SPm部分对NK-3受体的亲和力和/或通过防止其被某些蛋白水解酶降解，将SPm部分引入SP改变了亲本肽分子。

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