Zhang Y, Fredholm B B
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Biochem Pharmacol. 1994 Nov 29;48(11):2025-32. doi: 10.1016/0006-2952(94)90501-0.
In agreement with previous results, activation of adenosine A2 receptors was found to inhibit the exocytotic release of elastase and the oxidative burst induced by formyl-MetLeuPhe (fMLP) in human neutrophils. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) was more potent than adenosine (IC50 14 vs 64 nM). The effects of adenosine and NECA were not influenced by the A1-adenosine receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 300 nM), but were abolished by the non-selective adenosine receptor antagonist 9-chloro-2-(2-furanyl)-5,6-dihydro-[1,2,4]-triazolo[1,5]quinazolin -5-imine monomethanesulfonate (CGS 15943; 10 microM). Propentofylline per se caused a concentration-dependent inhibition of H2O2 production. At 100 microM propentofylline significantly enhanced the effect of adenosine, but not that of NECA. This effect of propentofylline was shared by the known uptake inhibitor dipyridamole. Neither adenosine nor propentofylline altered fMLP-induced inositol-(1,4,5)-trisphosphate (IP3) formation. The results demonstrate that propentofylline can counteract neutrophil activation, at least partly by enhancing the action of adenosine through blocking its removal, and that the effect is exerted at a step after the initial receptor events.
与先前的结果一致，研究发现腺苷A2受体的激活可抑制人中性粒细胞中弹性蛋白酶的胞吐释放以及甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）诱导的氧化爆发。腺苷类似物5'-N-乙基甲酰胺基腺苷（NECA）比腺苷更有效（IC50分别为14 nM和64 nM）。腺苷和NECA的作用不受A1-腺苷受体选择性拮抗剂1,3-二丙基-8-环戊基黄嘌呤（DPCPX；300 nM）的影响，但可被非选择性腺苷受体拮抗剂9-氯-2-（2-呋喃基）-5,6-二氢-[1,2,4]-三唑并[1,5]喹唑啉-5-亚胺单甲磺酸盐（CGS 15943；10 μM）消除。己酮可可碱本身可引起过氧化氢生成的浓度依赖性抑制。在100 μM时，己酮可可碱显著增强了腺苷的作用，但未增强NECA的作用。己酮可可碱的这种作用与已知的摄取抑制剂双嘧达莫相同。腺苷和己酮可可碱均未改变fMLP诱导的肌醇-（1,4,5）-三磷酸（IP3）的形成。结果表明，己酮可可碱可至少部分地通过阻止腺苷的清除来增强其作用，从而抵消中性粒细胞的激活，并且该作用在初始受体事件之后的一个步骤发挥。
