Biological Research Laboratories III, Daiichi Sankyo Co., Ltd., Japan.
J Pharmacol Sci. 2009 Nov;111(3):317-21. doi: 10.1254/jphs.09196sc.
A pyrazolone compound acting as a formyl peptide receptor (FPR) 2/ALX-selective agonist has been reported, but its pharmacological activities on human FPRs (hFPRs) and mouse FPRs (mFprs) have not been well demonstrated. In this study, we found that this compound, designated as compound A, induced concentration-dependent calcium flux not only in Chinese hamster ovary (CHO) cells expressing hFPR2/ALX but also in cells expressing hFPR1, mFpr1, or mFpr2. It also induced the receptor internalization of hFPR1 and hFPR2/ALX and, accordingly, induced calcium influx and chemotactic responses in both human and mouse neutrophils. Our study revealed that compound A is in fact an FPR1 and FPR2/ALX dual agonist.
一种作为甲酰肽受体（FPR）2/ALX 选择性激动剂的吡唑酮化合物已被报道，但它在人源 FPR（hFPR）和鼠源 FPR（mFpr）上的药理学活性尚未得到很好的证明。在这项研究中，我们发现这种化合物，命名为化合物 A，不仅在表达 hFPR2/ALX 的中国仓鼠卵巢（CHO）细胞中，而且在表达 hFPR1、mFpr1 或 mFpr2 的细胞中，均能诱导浓度依赖性的钙离子流。它还诱导 hFPR1 和 hFPR2/ALX 的受体内化，从而在人和鼠的中性粒细胞中诱导钙离子内流和趋化反应。我们的研究表明，化合物 A 实际上是一种 FPR1 和 FPR2/ALX 的双重激动剂。
