St Pierre Liam, Flight Simone, Masci Paul P, Hanchard Kim J, Lewis Richard J, Alewood Paul F, de Jersey John, Lavin Martin F
The Queensland Institute of Medical Research, Brisbane, Australia.
Biochimie. 2006 Dec;88(12):1923-31. doi: 10.1016/j.biochi.2006.06.014. Epub 2006 Aug 4.
The venom from Australian elapid snakes contains a complex mixture of polypeptide toxins that adversely affect multiple homeostatic systems within their prey in a highly specific and targeted manner. Included in these toxin families are the recently described venom natriuretic peptides, which display similar structure and vasoactive functions to mammalian natriuretic peptides. This paper describes the identification and detailed comparative analysis of the cDNA transcripts coding for the mature natriuretic peptide from a total of nine Australian elapid snake species. Multiple isoforms were identified in a number of species and represent the first description of a natriuretic peptide from the venom gland for most of these snakes. Two distinct natriuretic peptide isoforms were selected from the common brown snake (Pseudonaja textilis), PtNP-a, and the mulga (Pseudechis australis), PaNP-c, for recombinant protein expression and functional analysis. Only one of these peptides, PtNP-a, displayed cGMP stimulation indicative of normal natriuretic peptide activity. Interestingly, both recombinant peptides demonstrated a dose-dependent inhibition of angiotensin converting enzyme (ACE) activity, which is predictive of the vasoactive effects of the toxin. The natriuretic peptides, however, did not possess any coagulopathic activity, nor did they inhibit or potentiate thrombin, adenosine diphosphate or arachidonic acid induced platelet aggregation. The data presented in this study represent a significant resource for understanding the role of various natriuretic peptides isoforms during the envenomation process by Australian elapid snakes.
澳大利亚眼镜蛇科蛇类的毒液含有多种多肽毒素的复杂混合物，这些毒素以高度特异性和靶向性的方式对猎物的多个体内平衡系统产生不利影响。这些毒素家族包括最近描述的毒液利钠肽，它们与哺乳动物利钠肽具有相似的结构和血管活性功能。本文描述了对来自总共9种澳大利亚眼镜蛇科蛇类的成熟利钠肽编码的cDNA转录本的鉴定和详细比较分析。在许多物种中鉴定出了多种异构体，这是大多数这些蛇毒液腺中利钠肽的首次描述。从普通棕蛇（Pseudonaja textilis）中选择了两种不同的利钠肽异构体PtNP-a，以及从穆尔加蛇（Pseudechis australis）中选择了PaNP-c，用于重组蛋白表达和功能分析。这些肽中只有一种PtNP-a表现出cGMP刺激，表明具有正常的利钠肽活性。有趣的是，两种重组肽都表现出对血管紧张素转换酶（ACE）活性的剂量依赖性抑制，这预示着毒素的血管活性作用。然而，利钠肽不具有任何凝血病变活性，它们也不抑制或增强凝血酶、二磷酸腺苷或花生四烯酸诱导的血小板聚集。本研究中提供的数据是理解各种利钠肽异构体在澳大利亚眼镜蛇科蛇类毒液注入过程中作用的重要资源。
