Ziganshina L E, Ziganshin A U, Hoyle C H, Burnstock G
Department of Anatomy and Developmental Biology, University College London, UK.
Inflamm Res. 1996 Feb;45(2):96-102. doi: 10.1007/BF02265122.
ATP-induced inflammation was investigated using subplantar injection in the mouse hind paw. The order of efficacy of purinoceptor agonists for inducing paw oedema (30 nmol per paw) was ATP = alpha, beta-methylene ATP = 2-methylthio ATP > adenosine > UTP > ADP > AMP. Diadenosine polyphosphates effectively induced paw oedema formation with an order of efficacy of: P1,P4-di(adenosine-5')tetraphosphate = P1,P5-di(adenosine-5')-pentaphosphate = P1,P6-di(adenosine-5')hexaphosphate >>ATP = P1,P3-di(adenosine-5')triphosphate > P1,P2-di(adenosine-5')pyrophosphate. Systemic administration of P2-purinoceptor antagonists (30-100 mu mol/kg), suramin, 4,4'-diisothiocyanatostilbene-2,2'-disulphonate, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid and cibacron blue, reduced the intensity of ATP-induced oedema. At 30 mu mol/kg 8-(p-sulfophenyl)theophylline (non-selective adenosine receptor antagonist), 3,7-dimethyl-1,1-propargylxanthine (adenosine A2 receptor antagonist), triprolidine (histamine H1 receptor antagonist), ranitidine (histamine H2 receptor antagonist) and ketanserin (5-hydroxytryptamine 5-HT2 receptor antagonist), but neither 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1 receptor antagonist), nor indomethacin (cyclooxygenase inhibitor) inhibited the ATP-induced swelling. Topical (100 nmol per paw), but not systemic (100 mu mol/kg) administration of NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) reduced the intensity of the ATP-induced paw oedema. These results show that ATP can induce an inflammatory oedematous reaction and contribute to our understanding of the underlying mechanisms.
通过在小鼠后爪足底注射来研究ATP诱导的炎症。嘌呤受体激动剂诱导爪肿胀（每爪30 nmol）的效力顺序为：ATP = α,β-亚甲基ATP = 2-甲硫基ATP > 腺苷 > UTP > ADP > AMP。二腺苷多磷酸有效地诱导爪肿胀形成，效力顺序为：P1,P4-二（腺苷-5'）四磷酸 = P1,P5-二（腺苷-5'）五磷酸 = P1,P6-二（腺苷-5'）六磷酸 >> ATP = P1,P3-二（腺苷-5'）三磷酸 > P1,P2-二（腺苷-5'）焦磷酸。全身性给予P2-嘌呤受体拮抗剂（30 - 100 μmol/kg），苏拉明、4,4'-二异硫氰酸根合芪-2,2'-二磺酸盐、磷酸吡哆醛-6-偶氮苯-2',4'-二磺酸和汽巴蓝，可降低ATP诱导的肿胀强度。在30 μmol/kg时，8-（对磺苯基）茶碱（非选择性腺苷受体拮抗剂）、3,7-二甲基-1,1-炔丙基黄嘌呤（腺苷A2受体拮抗剂）、曲普利啶（组胺H1受体拮抗剂）、雷尼替丁（组胺H2受体拮抗剂）和酮色林（5-羟色胺5-HT2受体拮抗剂），但8-环戊基-1,3-二丙基黄嘌呤（腺苷A1受体拮抗剂）和吲哚美辛（环氧化酶抑制剂）均未抑制ATP诱导的肿胀。局部（每爪100 nmol）而非全身性（100 μmol/kg）给予NG-硝基-L-精氨酸甲酯（一氧化氮合酶抑制剂）可降低ATP诱导的爪肿胀强度。这些结果表明ATP可诱导炎症性水肿反应，并有助于我们理解其潜在机制。
