Sarafotoxin S6c is a peptide toxin that specifically activates the endothelin B receptor[1]. Sarafotoxin S6c binds with high affinity to the endothelin B receptor and triggers its downstream signaling pathway, leading to the contraction of vascular smooth muscle; this effect is independent of the integrity of the vascular endothelium[2]. Sarafotoxin S6c is also used to study the role of the endothelin system in cardiovascular physiology and pathological processes, including investigations into disease mechanisms such as pulmonary arterial hypertension[3-4].
In vitro, pretreatment of human hepatic myofibroblastic Ito cells with Sarafotoxin S6c (100nM), followed by stimulation with human serum (2–5%) or platelet-derived growth factor-BB (PDGF-BB; 20ng/ml) for 30 hours, resulted in significant inhibition of DNA synthesis and cell proliferation. This was accompanied by reduced mitogen-activated protein kinase (MAP kinase) activity and decreased c-jun mRNA expression[5].
In vivo, a single intraplantar injection of Sarafotoxin S6c (3–30pmol/paw) in mice 30 minutes prior to administration did not significantly affect capsaicin (0.1μg/paw)-induced nociceptive responses and did not produce a hyperalgesic effect[6].
References:
[1] Bdolah A, Wollberg Z, Fleminger G, et al. SRTX-d, a new native peptide of the endothelin/sarafotoxin family. FEBS Lett. 1989 Oct 9;256(1-2):1-3.
[2] Mills RG, Ralston GB, King GF. The solution structure of sarafotoxin-c. Implications for ligand recognition by endothelin receptors. J Biol Chem. 1994 Sep 23;269(38):23413-9.
[3] Wollberg Z, Bdolah A, Kochva E. Vasoconstrictor effects of sarafotoxins in rabbit aorta: structure-function relationships. Biochem Biophys Res Commun. 1989 Jul 14;162(1):371-6.
[4] Wollberg Z, Bdolah A, Galron R, et al. Contractile effects and binding properties of endothelins/sarafotoxins in the guinea pig ileum. Eur J Pharmacol. 1991 May 30;198(1):31-6.
[5] Mallat A, Fouassier L, Préaux AM, et al. Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells. An endothelin B receptor-mediated pathway. J Clin Invest. 1995 Jul;96(1):42-9.
[6] Piovezan AP, D'Orléans-Juste P, Tonussi CR, Rae GA. Effects of endothelin-1 on capsaicin-induced nociception in mice. Eur J Pharmacol. 1998 Jun 12;351(1):15-22.
Sarafotoxin S6c是一种能够特异性激活内皮素B受体的肽类毒素[1]。Sarafotoxin S6c可以高效地与内皮素B受体结合并激活其下游信号通路，进而引起血管平滑肌收缩，该作用不依赖于血管内皮的完整性[2]。Sarafotoxin S6c也被用于研究内皮素系统在心血管生理和病理过程中的作用，包括在肺动脉高压等疾病机制探索中的应用[3-4]。
在体外，Sarafotoxin S6c（100nM）预处理人肝肌纤维母细胞性Ito细胞，随后以人血清（2–5%）或血小板衍生生长因子-BB（PDGF-BB；20ng/ml）刺激30小时，Sarafotoxin S6c显著抑制DNA合成及细胞增殖，同时降低丝裂原活化蛋白激酶（MAP kinase）活性和c-jun mRNA表达[5]。
在体内，Sarafotoxin S6c（3-30pmol/paw）单次足底注射处理小鼠30分钟，对辣椒素（0.1μg/爪）诱导的伤害性反应无显著影响，且不产生痛觉过敏效应[6]。