Proctor Lavinia M, Moore Tyson A, Monk Peter N, Sanderson Sam D, Taylor Stephen M, Woodruff Trent M
School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
Int Immunopharmacol. 2009 Jun;9(6):800-6. doi: 10.1016/j.intimp.2009.03.002. Epub 2009 Mar 12.
In the rat, C5a infusion mediates well-defined effects including hypotension and neutropenia. Conversely, the comparative effect of C3a in the rat is not yet defined. In the current study, we have investigated C3a receptor (C3aR) activation in the rat, using recombinant human C3a, the C3aR agonist WWGKKYRASKLGLAR, which is a C-terminal analogue of C3a, and a nonpeptide C3aR antagonist SB-290157, as pharmacological tools. In vitro, C3a and WWGKKYRASKLGLAR selectively bound to C3aRs and induced degranulation of C3aR-transfected RBL-2H3 cells. C3a or WWGKKYRASKLGLAR-induced degranulation was dose-dependently antagonized in a surmountable fashion by the nonpeptide C3aR antagonist. Intravenous infusion of C3a and WWGKKYRASKLGLAR to rats induced a rapid, transient and concentration-dependent hypertensive response, which was mediated by C3aR-induced prostanoid release. C3a and WWGKKYRASKLGLAR caused a small drop in circulating neutrophils, but a rise in circulating neutrophils was evident after 90-120 min. In contrast to C3a, C5a infusion resulted in hypotension, and rapid and transient neutropenia. These results demonstrate that C3a and C5a mediate distinct effects on blood pressure and circulating polymorphonuclear leukocytes in the rat.
在大鼠中，输注C5a可介导明确的效应，包括低血压和中性粒细胞减少。相反，C3a在大鼠中的相应作用尚未明确。在本研究中，我们使用重组人C3a、C3aR激动剂WWGKKYRASKLGLAR（一种C3a的C末端类似物）和非肽C3aR拮抗剂SB - 290157作为药理学工具，研究了大鼠体内C3a受体（C3aR）的激活情况。在体外，C3a和WWGKKYRASKLGLAR选择性地与C3aR结合，并诱导C3aR转染的RBL - 2H3细胞脱颗粒。非肽C3aR拮抗剂能以可克服的方式剂量依赖性地拮抗C3a或WWGKKYRASKLGLAR诱导的脱颗粒。给大鼠静脉输注C3a和WWGKKYRASKLGLAR可诱导快速、短暂且浓度依赖性的高血压反应，这是由C3aR诱导的类前列腺素释放介导的。C3a和WWGKKYRASKLGLAR使循环中性粒细胞略有减少，但90 - 120分钟后循环中性粒细胞明显增多。与C3a不同，输注C5a导致低血压以及快速且短暂的中性粒细胞减少。这些结果表明，C3a和C5a对大鼠的血压和循环多形核白细胞介导不同的效应。
