Pharmacological Effects of Two Novel Bombesin-Like Peptides from the Skin Secretions of Chinese Piebald Odorous Frog (Odorrana schmackeri) and European Edible Frog (Pelophylax kl. esculentus) on Smooth Muscle.

Pharmacological Effects of Two Novel Bombesin-Like Peptides from the Skin Secretions of Chinese Piebald Odorous Frog (Odorrana schmackeri) and European Edible Frog (Pelophylax kl. esculentus) on Smooth Muscle.
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DOI:
10.3390/molecules22101798
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发表时间:
2017-10-23
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Wang L
Wang L
中科院分区:
其他
文献类型:
--
作者:
Zhou X;Ma C;Zhou M;Zhang Y;Xi X;Zhong R;Chen T;Shaw C;Wang L

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蛙皮素样肽(Bombesin-like peptides)是从多种两栖动物皮肤分泌物中发现的一类多肽,具有刺激平滑肌收缩、调节摄食等多种生物学功能。在这里,我们报告了两个新的蛙皮素样肽,蛙皮素-OS和蛙皮素-PE,这是从臭蛙和Pelophylax kl。esculentus,分别。通过高效液相色谱(HPLC)和串联质谱(MS/MS)对成熟肽进行鉴定和结构确认。随后,在膀胱、子宫和回肠中测定这些纯化的化学合成肽对平滑肌的作用。人工合成的复制品显示对这些组织具有显著的药理作用。蛙皮素-OS对膀胱、子宫和回肠的EC 50值分别为10.8 nM、33.64 nM和12.29 nM。此外,与蛙皮素-OS相比,蛙皮素-PE对回肠平滑肌和子宫平滑肌显示出相似的收缩活性,但对膀胱平滑肌具有更高的效力。蛙皮素-OS对膀胱的EC 50值比蛙皮素-PE的EC 50值小约1000倍。这表明蛙皮素-OS和蛙皮素-PE对其受体具有独特的结合特性。蛙皮素-OS的前体与蛙皮素样肽odorranain-BLP-5的前体同源,并且蛙皮素-PE属于蛙皮素亚家族。我们确定了蛙皮素-OS和蛙皮素-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,也为人类健康提供新的药物。
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 EC50 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 EC50 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.
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