反应选择性C5a激动剂：对大鼠中性粒细胞减少和低血压的不同影响
Response-selective C5a agonists: differential effects on neutropenia and hypotension in the rat.
作者信息
Short A J, Paczkowski N J, Vogen S M, Sanderson S D, Taylor S M
机构信息
Department of Physiology and Pharmacology, University of Queensland, St Lucia, Queensland 4072, Australia.
出版信息
Br J Pharmacol. 1999 Oct;128(3):511-4. doi: 10.1038/sj.bjp.0702847.
Some in vivo activities of two complement C5a agonist analogues have been evaluated by measuring changes in blood pressure and neutropenia in the rat and comparing the results with their receptor affinities in peritoneal macrophages and polymorphonuclear leucocytes (PMNs). In vitro C5a receptor (C5aR) binding experiments showed that YSFKPMPLaR and YSFKD(NMeNle)PlaR had similar affinities for the macrophage C5aR (IC50 0.2, 0.1 microM respectively). In PMNs, the affinity of YSFKPMPLaR (IC50 0.1 microM) was similar to that in macrophages, whereas the affinity of YSFKD(NMeNle)PLaR for the PMN C5aR was >100 microM. Given i.v., YSFKD(NMeNle)PLaR had similar activity to YSFKPMPLaR on blood pressure but did not cause neutropenia. These results demonstrate selectivity of a new C5a agonist in vitro, which is paralleled in vivo. The results suggest the possibility of developing selective agonists of C5a for in vivo use in humans.
通过测量大鼠血压变化和中性粒细胞减少情况，并将结果与其在腹膜巨噬细胞和多形核白细胞（PMNs）中的受体亲和力进行比较，对两种补体C5a激动剂类似物的一些体内活性进行了评估。体外C5a受体（C5aR）结合实验表明，YSFKPMPLaR和YSFKD（NMeNle）PlaR对巨噬细胞C5aR具有相似的亲和力（IC50分别为0.2、0.1 microM）。在PMNs中，YSFKPMPLaR的亲和力（IC50为0.1 microM）与巨噬细胞中的相似，而YSFKD（NMeNle）PlaR对PMN C5aR的亲和力>100 microM。静脉注射时，YSFKD（NMeNle）PlaR在血压方面与YSFKPMPLaR具有相似的活性，但不会导致中性粒细胞减少。这些结果证明了一种新型C5a激动剂在体外具有选择性，在体内也与之平行。结果表明开发用于人类体内的C5a选择性激动剂具有可能性。
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