Pharmacological characterization of nociceptin receptor: an in vitro study.
Pharmacological characterization of nociceptin receptor: an in vitro study.
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伤害感受素受体的药理学特征：体外研究。
DOI：
10.1139/y97-055
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发表时间：
1997
影响因子：
2.1
通讯作者：
D. Regoli
中科院分区：
文献类型：
--
作者：
G. Calo’;A. Rizzi;M. Bodin;W. Neugebauer;S. Salvadori;R. Guerrini;C. Bianchi;D. Regoli
新发现的神经肽伤害感受肽 (NC)（又名孤啡肽 FQ）经过了测试，了解其潜在的直接作用以及其改变体外悬浮的几个离体器官的电诱发收缩的能力。 NC 在几种制剂中作为平滑肌的兴奋剂和抑制剂均无活性，而它抑制小鼠输精管和豚鼠回肠中由电场刺激引起的收缩。 NC 在两种制剂中显示出相同的效力 (IC50 = 10 nM)。然而，它在小鼠输精管中的效果（最大效果-80%）明显比在豚鼠回肠中的效果（最大效果-50%）更有效。 NC在两种制剂中发挥的抑制作用不受纳洛酮或更选择性阿片受体拮抗剂的影响。此外，通过截短C端序列，设计了NC片段。随后在小鼠输精管和豚鼠回肠中测试这些片段：NC(1-13)-NH2 是最小的肽，与天然肽保持相同的功效和效力。最后，通过用酪氨酸取代苯丙氨酸1残基来修饰NC-NH2及其片段NC(1-13)-NH2和NC(1-9)-NH2。这些肽在豚鼠回肠中进行了测试，它们表现为混合 NC-阿片受体激动剂（[Tyr1]NC-NH2 和 [Tyr1]NC(1-13)-NH2）或纯阿片受体激动剂（[Tyr1]NC(1-9)-NH2）。 总之，本文证明电刺激的小鼠输精管和豚鼠回肠可以用作用于研究 NC 和相关化合物药理学的灵敏生物测定。
The newly discovered neuropeptide nociceptin (NC) (alias orphanin FQ) was tested for its potential direct effects as well as for its ability to modify the electrically evoked contractions in several isolated organs suspended in vitro. NC was inactive both as stimulant and as inhibitor of smooth muscle in several preparations, whereas it inhibited the contractions induced by electrical field stimulation in the mouse vas deferens and guinea pig ileum. NC showed the same potency (IC50 = 10 nM) in the two preparations. However, it was significantly more effective in the mouse vas deferens (maximal effect -80%) than in the guinea pig ileum (maximal effect -50%). The inhibitory effect exerted by NC in the two preparations was not affected by naloxone or more selective opioid receptor antagonists. Moreover, by truncation of C-terminal sequences, NC fragments were designed. These fragments were subsequently tested in the mouse vas deferens and in the guinea pig ileum: NC(1-13)-NH2 was the smallest peptide maintaining the same efficacy and potency as the natural peptide. Finally, NC-NH2 and its fragments NC(1-13)-NH2 and NC(1-9)-NH2 were modified by substituting the phenylalanine 1 residue with a tyrosine. These peptides were tested in the guinea pig ileum, where they behaved as mixed NC-opioid receptor agonists ([Tyr1]NC-NH2 and [Tyr1]NC(1-13)-NH2) or as pure opioid receptor agonists ([Tyr1]NC(1-9)-NH2. In conclusion, the present paper demonstrated that the electrically stimulated mouse vas deferens and guinea pig ileum can be used as a sensitive bioassay for studying the pharmacology of NC and related compounds.
DOI：
10.1073/pnas.82.1.236
发表时间：
1985-01-01
影响因子：
11.1
作者：
PELTON, JT;GULYA, K;YAMAMURA, HI
通讯作者：
YAMAMURA, HI