del Balzo U, Polley M J, Levi R
Department of Pharmacology, Cornell University Medical College, New York, New York.
J Pharmacol Exp Ther. 1989 Mar;248(3):1003-9.
Guinea pig ileum is the classical experimental model for assessing the biological activity of complement-derived anaphylatoxins. Nevertheless, it is still at issue whether C3a-induced ileal contraction is entirely dependent on histamine release. We report that the contraction of the intestinal smooth muscle in response to C3a is characterized by two components, fast and slow, whose incidence and amplitude is strictly dependent on C3a concentration; the larger the concentration of C3a, the greater the incidence and magnitude of the fast component and the less frequent the slow component. The fast and slow components were characterized by a sigmoid and bell-shaped concentration-response curve, respectively. The fast component was associated with the release of endogenous histamine, increased in magnitude with the quantity of histamine released and was prevented by the histamine H1 receptor antagonist pyrilamine. On the contrary, there was no correlation between the quantity of histamine released by C3a and the magnitude of the slow component. Instead, the slow component was associated with the release of PGE2 and was prevented by the cyclooxygenase inhibitor indomethacin. Neither component was affected by the leukotriene receptor antagonist FPL 55712. Our data indicate that C3a-induced ileal contraction is partially histamine dependent in that histamine mediates only the fast component, whereas cyclooxygenase metabolites are responsible for the slow component.
豚鼠回肠是评估补体衍生过敏毒素生物活性的经典实验模型。然而，C3a诱导的回肠收缩是否完全依赖于组胺释放仍存在争议。我们报告，C3a引起的肠道平滑肌收缩具有快速和缓慢两个成分，其发生率和幅度严格依赖于C3a浓度；C3a浓度越高，快速成分的发生率和幅度越大，缓慢成分的频率越低。快速和缓慢成分分别以S形和钟形浓度-反应曲线为特征。快速成分与内源性组胺释放有关，其幅度随组胺释放量增加而增加，并被组胺H1受体拮抗剂吡苄明阻断。相反，C3a释放的组胺量与缓慢成分的幅度之间没有相关性。相反，缓慢成分与PGE2释放有关，并被环氧化酶抑制剂吲哚美辛阻断。两种成分均不受白三烯受体拮抗剂FPL 55712影响。我们的数据表明，C3a诱导的回肠收缩部分依赖于组胺，因为组胺仅介导快速成分，而环氧化酶代谢产物则负责缓慢成分。
