Wise H
Department of Pharmacology, The Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories.
Prostaglandins Leukot Essent Fatty Acids. 1998 Jan;58(1):77-84. doi: 10.1016/s0952-3278(98)90133-8.
The inhibitory activity of prostaglandin E2 (PGE2) on rat neutrophil aggregation has been studied using the EP4-receptor antagonist AH23848B. While AH23848B antagonized the ability of PGE2 to inhibit neutrophil aggregation stimulated by platelet-activating factor (PAF), AH23848B showed agonist activity when neutrophils were stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, AH23848B showed weak stimulation of adenylyl cyclase activity and inhibited PGE2-stimulated [3H]cyclic AMP production by rat neutrophils, therefore AH23848B appears to be a partial agonist at EP4-receptors. These results suggest that rat neutrophils possess both inhibitory EP2- and EP4-receptors, and that FMLP-stimulated neutrophil aggregation is more highly coupled to inhibition by EP4-receptor activation than is PAF-stimulated neutrophil aggregation.
利用EP4受体拮抗剂AH23848B研究了前列腺素E2（PGE2）对大鼠中性粒细胞聚集的抑制活性。虽然AH23848B拮抗了PGE2抑制血小板活化因子（PAF）刺激的中性粒细胞聚集的能力，但当用N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）刺激中性粒细胞时，AH23848B表现出激动剂活性。此外，AH23848B对腺苷酸环化酶活性有微弱刺激作用，并抑制PGE2刺激的大鼠中性粒细胞[3H]环磷酸腺苷（cAMP）生成，因此AH23848B似乎是EP4受体的部分激动剂。这些结果表明，大鼠中性粒细胞同时具有抑制性的EP2和EP4受体，并且与PAF刺激的中性粒细胞聚集相比，FMLP刺激的中性粒细胞聚集与EP4受体激活介导的抑制作用的偶联性更高。
