Department of Nutrition, Henry Fok School of Food Science and Engineering, Shaoguan University, Shaoguan 512005, China.
Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
Molecules. 2017 Oct 23;22(10):1798. doi: 10.3390/molecules22101798.
Bombesin-like peptides, which were identified from a diversity of amphibian skin secretions, have been demonstrated to possess several biological functions such as stimulation of smooth muscle contraction and regulation of food intake. Here, we report two novel bombesin-like peptides, bombesin-OS and bombesin-PE, which were isolated from Odorrana schmackeri and Pelophylax kl. esculentus, respectively. The mature peptides were identified and structurally confirmed by high performance Scliquid chromatography (HPLC) and tandem mass spectrometry (MS/MS). Subsequently, the effects of these purified chemically-synthetic peptides on smooth muscle were determined in bladder, uterus, and ileum. The synthetic replications were revealed to have significant pharmacological effects on these tissues. The EC values of bombesin-OS for bladder, uterus and ileum, were 10.8 nM, 33.64 nM, and 12.29 nM, respectively. Furthermore, compared with bombesin-OS, bombesin-PE showed similar contractile activity on ileum smooth muscle and uterus smooth muscle, but had a higher potency on bladder smooth muscle. The EC value of bombesin-OS for bladder was around 1000-fold less than that of bombesin-PE. This suggests that bombesin-OS and bombesin-PE have unique binding properties to their receptors. The precursor of bombesin-OS was homologous with that of a bombesin-like peptide, odorranain-BLP-5, and bombesin-PE belongs to the ranatensin subfamily. We identified the structure of bombesin-OS and bombesin-PE, two homologues peptides whose actions may provide a further clue in the classification of ranid frogs, also in the provision of new drugs for human health.
蛙皮素样肽最初从多种两栖动物皮肤分泌物中被发现，已被证明具有多种生物学功能，如刺激平滑肌收缩和调节摄食。在这里，我们报道了两种从 Odorrana schmackeri 和 Pelophylax kl. esculentus 中分离得到的新型蛙皮素样肽，分别命名为 bombesin-OS 和 bombesin-PE。通过高效液相色谱（HPLC）和串联质谱（MS/MS）鉴定和结构确证了成熟肽。随后，测定了这些纯化的化学合成肽对膀胱、子宫和回肠平滑肌的影响。这些合成复制物对这些组织具有显著的药理学作用。Bombesin-OS 对膀胱、子宫和回肠的 EC 值分别为 10.8 nM、33.64 nM 和 12.29 nM。此外，与 bombesin-OS 相比，bombesin-PE 对回肠平滑肌和子宫平滑肌表现出相似的收缩活性，但对膀胱平滑肌的效力更高。Bombesin-OS 对膀胱的 EC 值约为 bombesin-PE 的 1000 倍。这表明 bombesin-OS 和 bombesin-PE 与其受体具有独特的结合特性。Bombesin-OS 的前体与一种蛙皮素样肽 odorranain-BLP-5 同源，而 bombesin-PE 属于 ranatensin 亚科。我们鉴定了 bombesin-OS 和 bombesin-PE 的结构，这两种同源肽的作用可能为蛙类的分类提供进一步的线索，并为人类健康提供新的药物。
