有证据表明存在两种不同的P2嘌呤受体，它们参与大鼠肛门尾骨肌平滑肌的收缩。
Evidence for two distinct P2-purinoceptors subserving contraction of the rat anococcygeus smooth muscle.
作者信息
Najbar A T, Li C G, Rand M J
机构信息
Department of Medical Laboratory Science, RMIT University, Melbourne, Vic., Australia.
出版信息
Br J Pharmacol. 1996 Jun;118(3):537-42. doi: 10.1111/j.1476-5381.1996.tb15435.x.
Abstract
- The effects of the P2-purinoceptor agonists, adenosine 5'-triphosphate (ATP), alpha, beta-methylene ATP (alpha, beta-MeATP), beta, gamma-methylene ATP (beta, gamma-MeATP), L-beta, gamma-methylene ATP (L-beta, gamma-MeATP), adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), and 2-methylthio ATP (2-MeSATP) were investigated on the isometric tension of the rat anococcygeus muscle. 2. Non-cumulative additions of ATP (100-1500 microM), alpha, beta-MeATP (1-300 microM), beta, gamma-MeATP (10-300 microM), L-beta, gamma-MeATP (3-100 microM) and ADP beta S (1-100 microM) produced concentration-dependent contractions, whereas 2-MeSATP (1-100 microM) had no effect. The rank order of potency was alpha, beta-MeATP > L-beta, gamma-MeATP > or = ADP beta S > beta, gamma-MeATP > > ATP > 2-MeSATP. 3. Contractions to cumulative additions of ATP, alpha, beta-MeATP, beta, gamma-MeATP and L-beta, gamma-MeATP were subject to desensitization whilst those to ADP beta S were unaffected. 4. Contractions to ATP, alpha, beta-MeATP, beta, gamma-MeATP and ADP beta S were abolished by the non-selective P2X/. P2Y-purinoceptor antagonist, suramin (100 microM). In contrast, contractions to ATP, alpha, beta-MeATP and beta, gamma-MeATP were not affected by the non-selective P1-purinoceptor antagonist 8-(p-sulphophenyl)-theophylline (8SPT, 30 microM). Blockade of P2X-purinoceptors with the selective P2X-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM) or desensitization with L-beta, gamma-MeATP (10 microM) abolished contractions to alpha, beta-MeATP, but enhanced those to ADP beta S. The P2Y-purinoceptor antagonist, reactive blue 2 (RB2, 100 microM) enhanced contractions to ATP and alpha, beta-MeATP but abolished those to ADP beta S. 5. Simultaneous addition of alpha, beta-MeATP and ADP beta S produced an additive contraction. 6. The findings suggest that in the rat anococcygeus, smooth muscle cells are endowed with two distinct P2-purinoceptors which subserve contractions: a P2X-purinoceptor activated by ATP and its analogues, and another type of P2-purinoceptor activated by ADP beta S.
摘要
- 研究了P2嘌呤受体激动剂三磷酸腺苷（ATP）、α,β-亚甲基ATP（α,β-MeATP）、β,γ-亚甲基ATP（β,γ-MeATP）、L-β,γ-亚甲基ATP（L-β,γ-MeATP）、腺苷-5'-O-(2-硫代二磷酸)（ADPβS）和2-甲硫基ATP（2-MeSATP）对大鼠肛门尾骨肌等长张力的影响。2. 非累积添加ATP（100 - 1500微摩尔）、α,β-MeATP（1 - 300微摩尔）、β,γ-MeATP（10 - 300微摩尔）、L-β,γ-MeATP（3 - 100微摩尔）和ADPβS（1 - 100微摩尔）可产生浓度依赖性收缩，而2-MeSATP（1 - 100微摩尔）无作用。效力顺序为α,β-MeATP > L-β,γ-MeATP ≥ ADPβS > β,γ-MeATP >> ATP > 2-MeSATP。3. 对ATP、α,β-MeATP、β,γ-MeATP和L-β,γ-MeATP累积添加的收缩反应会发生脱敏，而对ADPβS的收缩反应不受影响。4. 非选择性P2X/P2Y嘌呤受体拮抗剂苏拉明（100微摩尔）可消除对ATP、α,β-MeATP、β,γ-MeATP和ADPβS的收缩反应。相比之下，非选择性P1嘌呤受体拮抗剂8-（对磺基苯基）茶碱（8SPT，30微摩尔）对ATP、α,β-MeATP和β,γ-MeATP的收缩反应无影响。用选择性P2X嘌呤受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸（PPADS，10微摩尔）阻断P2X嘌呤受体或用L-β,γ-MeATP（10微摩尔）脱敏可消除对α,β-MeATP的收缩反应，但增强对ADPβS的收缩反应。P2Y嘌呤受体拮抗剂反应性蓝2（RB2，100微摩尔）增强对ATP和α,β-MeATP的收缩反应，但消除对ADPβS的收缩反应。5. 同时添加α,β-MeATP和ADPβS可产生相加性收缩。6. 研究结果表明，在大鼠肛门尾骨肌中，平滑肌细胞具有两种不同的用于产生收缩的P2嘌呤受体：一种由ATP及其类似物激活的P2X嘌呤受体，以及另一种由ADPβS激活的P2嘌呤受体类型。
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