Patacchini R, Maggi C A
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
J Pharmacol Exp Ther. 1992 Apr;261(1):191-4.
The present study was undertaken to assess the activity of the neurokinin-2 (NK2) tachykinin receptor-selective antagonists MEN 10,376, L 659,877 and R 396 along with the NK2 receptor-selective ligand, MDL 28,564 on the isolated guinea pig gallbladder. None of the antagonists tested inhibited the response to the peptide CCK-8, although they competitively antagonized the contractile effect produced by NKA in the above tissue. The following rank order of potency was observed: MEN 10,376 (pKB = 6.77) greater than L 659,877 (pKB = 6.29) greater than R396 (pKB = 5.26). MEN 10,376 also antagonized the response to the NK3-selective agonist [MePhe7].NkB (10 microM), showing that the agonist activity of this peptide is due to NK2 receptor stimulation. On the other hand, MDL 28,564 had an agonist effect in the isolated gallbladder, its maximal effect approaching 58% of that to NKA. The results obtained using the above NK2 receptor-selective drugs in the guinea pig gallbladder was similar to that observed in other mammalian tissues bearing the NK2A receptor subtype, such as the endothelium-denuded rabbit pulmonary artery, the guinea pig bronchus and the circular muscle of the human colon and ileum. Therefore, we conclude that in the isolated guinea pig gallbladder tachykinins exert their contractile effect by activating NK2 receptors, which seem to belong to the NK2A receptor subtype.
本研究旨在评估神经激肽-2（NK2）速激肽受体选择性拮抗剂MEN 10,376、L 659,877和R 396以及NK2受体选择性配体MDL 28,564对离体豚鼠胆囊的作用。尽管所测试的拮抗剂竞争性拮抗了NKA在上述组织中产生的收缩效应，但没有一种拮抗剂能抑制对肽CCK-8的反应。观察到以下效价顺序：MEN 10,376（pKB = 6.77）＞L 659,877（pKB = 6.29）＞R396（pKB = 5.26）。MEN 10,376也拮抗了对NK3选择性激动剂[MePhe7].NkB（10 μM）的反应，表明该肽的激动剂活性是由于NK2受体刺激所致。另一方面，MDL 28,564在离体胆囊中具有激动剂作用，其最大效应接近NKA的58%。在豚鼠胆囊中使用上述NK2受体选择性药物获得的结果与在其他表达NK2A受体亚型的哺乳动物组织中观察到的结果相似，如去内皮兔肺动脉、豚鼠支气管以及人结肠和回肠的环形肌。因此，我们得出结论，在离体豚鼠胆囊中，速激肽通过激活NK2受体发挥收缩作用，这些受体似乎属于NK2A受体亚型。
