Reeves J J, Jones C A, Sheehan M J, Vardey C J, Whelan C J
Receptor Pharmacology Unit, Glaxo Wellcome Research & Development Ltd., Stevenage, Hertfordshire, UK.
Inflamm Res. 1997 May;46(5):180-4. doi: 10.1007/s000110050169.
To investigate the effects of adenosine receptor agonists and antagonists on 5-HT release from rat isolated pleural mast cells and on plasma protein extravasation in the skin of conscious rats. In vitro
Rat isolated pleural mast cells were loaded with [14C] 5-HT, sensitised with mouse monoclonal anti-DNP and then challenged with human serum albumin-DNP. DNP-stimulated 5-HT release from mast cells was determined. In vivo
Rats, loaded intravenously with [125I] human serum albumin, were injected intradermally with adenosine agonists at sites on the back. 30 min later plasma protein extravasation at each injection site was determined.
In isolated mast cells, each adenosine agonist enhanced DNP-induced 5-HT release, N6-(3-iodobenzyl)-5-(N-methyl-carboxamidoadenosine), (IB-MECA), being the most potent agonist. The adenosine A1/A2 antagonist, 8-phenyltheophylline (8-PT), had no effect on the response to IB-MECA. In contrast, 3-(4-amino-iodobenzyl)-8-[4-[[[carboxy]methyl]oxy]phenyl]-1-propylxanthi ne, (I-ABOPX), inhibited (pA2 6.2) the IB-MECA responses. In the skin of conscious rats, intradermal IB-MECA produced a marked plasma protein extravasation (PPE) which was mimicked by N6-2-(4-aminophenyl)-ethyladenosine (APNEA). The PPE produced by IB-MECA was not affected by either 8-PT or CGS15943A, but was virtually abolished by cyproheptadine and in rats pre-treated with Compound 48/80.
These results indicate that stimulation of adenosine A3 receptors both enhances degranulation in vitro and directly produces degranulation of rat mast cells in vivo.
研究腺苷受体激动剂和拮抗剂对大鼠离体胸膜肥大细胞5-羟色胺（5-HT）释放及清醒大鼠皮肤血浆蛋白外渗的影响。体外实验
用[14C]5-HT标记大鼠离体胸膜肥大细胞，用小鼠抗二硝基苯（DNP）单克隆抗体致敏，然后用人血清白蛋白-DNP激发。测定DNP刺激肥大细胞释放5-HT的情况。体内实验
给大鼠静脉注射[125I]人血清白蛋白，在背部皮内注射腺苷激动剂。30分钟后测定各注射部位的血浆蛋白外渗情况。
在离体肥大细胞中，每种腺苷激动剂均增强DNP诱导的5-HT释放，N6-(3-碘苄基)-5-(N-甲基-羧酰胺基腺苷)（IB-MECA）是最有效的激动剂。腺苷A1/A2拮抗剂8-苯甲基茶碱（8-PT）对IB-MECA的反应无影响。相反，3-(4-氨基碘苄基)-8-[4-[[[羧基]甲基]氧基]苯基]-1-丙基黄嘌呤（I-ABOPX）抑制（pA2 6.2）IB-MECA的反应。在清醒大鼠的皮肤中，皮内注射IB-MECA可引起明显的血浆蛋白外渗（PPE），N6-2-(4-氨基苯基)-乙基腺苷（APNEA）可模拟该反应。IB-MECA引起的PPE不受8-PT或CGS15943A的影响，但几乎被赛庚啶和用化合物48/80预处理的大鼠所消除。
这些结果表明，刺激腺苷A3受体在体外增强脱颗粒作用，并在体内直接引起大鼠肥大细胞脱颗粒。
