Two novel bombesin-like neuropeptides from the skin secretion of Pelophylax kl. esculentus: Ex vivo pharmacological characterization on rat smooth muscle types.
Two novel bombesin-like neuropeptides from the skin secretion of Pelophylax kl. esculentus: Ex vivo pharmacological characterization on rat smooth muscle types.
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DOI：
10.3389/fmolb.2022.953974
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发表时间：
2022
影响因子：
5
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哺乳动物蛙毒素样神经肽(BLPs)在生理和病理生理过程中起着重要的调节作用。蛙皮肤来源的BLPs具有较小的大小和N端不同的长度和序列，引起了许多研究人员的注意。然而，这些N-末端变异体和调节其药理作用的受体研究得很少，也不太清楚。本研究从杂交种Pelophylax KL的皮肤分泌物中分离到两个BLPs，分别为[Asn3，Lys6，Thr10，Phe13]3-14-蛙黄素和[Asn3，Lys6，Phe13]3-14-蛙黄素，其一级结构分别为NLGKQWATGHFM和NLGKQWAVGHFM。斯库伦特斯。两种BLPs的一级结构相似，仅在第八位有一个单一的氨基酸取代(苏氨酸到缬氨酸)，但它们具有非常不同的肌力，EC50值在22.64±9.7nM(N=8)到83.93±46.9nM(N=8)之间。[Asn3，Lys6，Thr10，Phe13]3-14-蛙素的效价约为[Asn3，Lys6，Phe13]3-14-蛙素的3倍。通过使用典型的蛙皮素受体拮抗剂对受体选择性的研究，发现[Asn3，Lys6，Thr10，Phe13]3-14-蛙皮素和[Asn3，Lys6，Phe13]3-14-蛙皮素对BB1和BB2受体均有亲和力。它们的收缩功能主要受大鼠膀胱上的BB1和BB2受体以及大鼠子宫肌条上的BB2单独调节。这些数据可能为蛙皮素受体的有效和选择性配体的设计提供新的见解。此外，[Asn3，Lys6，Thr10，Phe13]3-14-蛙黄素和[Asn3，Lys6，Phe13]3-14-蛙黄素对正常人细胞没有明显的溶血和毒性作用，提示这两种天然新型BLPs具有开发成为新药候选药物的巨大潜力。
Mammalian bombesin-like neuropeptides (BLPs) play an important role in regulation of physiological and pathophysiological processes. Frog skin-derived BLPs, of smaller size and diverse lengths and sequences at their N-terminus, have attracted the attention of many researchers. However, these N-terminal variants and the receptors modulating their pharmacological actions are poorly studied and less understood. In this study, two BLPs, namely, [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin with primary structures NLGKQWATGHFM and NLGKQWAVGHFM were isolated from the skin secretion of hybrid Pelophylax kl. esculentus. Both BLPs share a similar primary structure with only a single amino acid substitution at the eighth position (threonine to valine), while they have quite different myotropic potencies with EC50 values in the range of 22.64 ± 9.7 nM (N = 8) to 83.93 ± 46.9 nM (N = 8). The potency of [Asn3, Lys6, Thr10, Phe13]3–14-bombesin was approximately 3-fold higher than that of [Asn3, Lys6, Phe13]3–14-bombesin. Through the investigation of receptor selectivity using a canonical bombesin receptor antagonist, it was found that [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin had an affinity to both BB1 and BB2 receptors. Their contractile functions are mainly modulated by both BB1 and BB2 receptors on rat urinary bladder and BB2 alone on rat uterus smooth muscle preparations. These data may provide new insights into the design of potent and selective ligands for bombesin receptors. Moreover, [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin did not induce significant hemolysis and toxicity in normal human cells, suggesting that these two natural novel BLPs have great potential for development into new drug candidates.
DOI：
10.3390/molecules22101798
发表时间：
2017-10-23
期刊：
Molecules (Basel, Switzerland)
影响因子：
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作者：
Zhou X;Ma C;Zhou M;Zhang Y;Xi X;Zhong R;Chen T;Shaw C;Wang L
通讯作者：
Wang L