Improta G, Broccardo M, Severini C, Erspamer V
Institute of Medical Pharmacology, University of Rome, La Sapienza, Italy.
Peptides. 1996;17(6):1003-8. doi: 10.1016/0196-9781(96)00140-4.
We compared the in vitro and in vivo biological activities of PG-KII (pGlu-Pro-Asn-Pro-Asp-Glu-Phe-Val-Gly-Leu-Met-NH2), a new peptide belonging to the tachykinin family, related to kassinin, isolated and sequenced from extracts of the skin of the Australian myobatrachid frog Pseudophryne güntheri, with those of the well-known tachykinins [substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and kassinin (KASS)] to study its pharmacological and receptor profile. PG-KII always proved inactive in the in vitro and in vivo (gastric emptying) NK2 bioassays. It resulted equipotent to SP and more potent than KASS, NKA, and NKB in all in vitro smooth muscle preparations preferentially activated by the NK1-selective agonists. On an in vivo NK3 receptor-mediated function, gastric acid secretion, PG KII had a potency similar to that of NKB. In contracting guinea pig ileum, which contains NK1, NK2, NK3, and also new tachykinin receptor subtypes, PG-KII was more potent than SP, NKB, and NKA. The cholinergic antagonist, atropine, significantly reduced the guinea pig contractile activity of both PG-KII and NKB but not that of SP or NKA. Pretreatment with the NK1 selective antagonist, CP 96,345, and with the NK2-selective antagonist, MEN 10,376, modified neither the in vivo nor the in vitro effects of PG-KII. These findings indicate that PG-KII is neither an NK1 nor an NK2 receptor agonist but has a spectrum of biological actions close to that of the NK3 receptor agonists. PG-KII elicits strong contractile activity in guinea pig ileum. Administered centrally in the rat it regulates inhibition of gastric acid secretion.
我们比较了PG-KII（pGlu-Pro-Asn-Pro-Asp-Glu-Phe-Val-Gly-Leu-Met-NH2）的体外和体内生物学活性，PG-KII是一种属于速激肽家族的新肽，与蛙皮素相关，从澳大利亚沼蟾科青蛙冈瑟氏伪蛙皮肤提取物中分离并测序，同时将其与著名的速激肽[P物质（SP）、神经激肽A（NKA）、神经激肽B（NKB）和蛙皮素（KASS）]进行比较，以研究其药理学和受体特征。PG-KII在体外和体内（胃排空）NK2生物测定中始终被证明无活性。在所有优先被NK1选择性激动剂激活的体外平滑肌制剂中，它与SP等效，且比KASS、NKA和NKB更有效。在体内NK3受体介导的胃酸分泌功能方面，PG KII的效力与NKB相似。在收缩含有NK1、NK2、NK3以及新的速激肽受体亚型的豚鼠回肠时，PG-KII比SP、NKB和NKA更有效。胆碱能拮抗剂阿托品显著降低了PG-KII和NKB对豚鼠的收缩活性，但对SP或NKA没有影响。用NK1选择性拮抗剂CP 96,345和NK2选择性拮抗剂MEN 10,376预处理，既不改变PG-KII的体内作用也不改变其体外作用。这些发现表明，PG-KII既不是NK1受体激动剂也不是NK2受体激动剂，但其生物学作用谱与NK3受体激动剂相近。PG-KII在豚鼠回肠中引发强烈的收缩活性。在大鼠中枢给药时，它可调节胃酸分泌的抑制作用。
