三磷酸腺苷（ATP）在豚鼠小肠中的多种运动效应及其受P嘌呤受体拮抗剂磷酸吡哆醛 - 6 - 偶氮苯 - 2',4'-二磺酸的抑制作用
Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of the guinea-pig.
作者信息
Barthó Lorand, Undi Sarolta, Benkó Rita, Wolf Matyas, Lázár Zsofia, Lénárd Laszlo, Maggi Carlo A
机构信息
Department of Pharmacology and Pharmacotherapy, Division of Pharmacodynamics, University of Pécs Medical School, Pécs, Hungary.
出版信息
Basic Clin Pharmacol Toxicol. 2006 May;98(5):488-95. doi: 10.1111/j.1742-7843.2006.pto_369.x.
Adenosine 5'-triphosphate (ATP) may be an important neurotransmitter in the gastrointestinal tract. The present study examined the motor effects of exogenous ATP on longitudinally-oriented preparations of the guinea-pig isolated ileum and the influence of drugs on the ATP-induced responses. High micromolar concentrations of ATP caused two types of contraction, a phasic, cholinergic response and a tonic, tetrodotoxin-resistant contraction. The phasic contraction was reduced by hexamethonium (5x10(-5) M), but left uninfluenced by capsaicin tachyphylaxis or tachyphylaxis to alpha,beta-methylene ATP. The tonic response was resistant to atropine, hexamethonium, capsaicin, omega-conotoxin GVIA, or pretreatment with alpha,beta-methylene ATP. Both types of ATP-induced contraction were diminished or abolished by the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 3x10(-6) and 3x10(-5) M, respectively). In the precontracted, atropine-treated ileum ATP (10(-6)-10(-4) M) caused guanethidine-resistant relaxation. This response was not influenced by tetrodotoxin, omega-conotoxin GVIA, or NG-nitro-L-arginine, but was abolished by apamin (10(-7) M), and inhibited by PPADS (3x10(-5) M) or reactive blue 2 (10(-5) M), in a surmountable manner. A high degree of tachyphylaxis was observed with the relaxant effect of ATP (10(-5)-10(-4) M). A high concentration (3x10(-4) M) of PPADS failed to influence ileum contractions to exogenous acetylcholine or histamine. It is concluded that, in addition to its direct contractile action in the guinea-pig ileum, ATP can activate (partly preganglionic) cholinergic neurones, an effect whose mechanism is largely different from that of alpha,beta-methylene ATP. ATP also causes relaxation by a direct, probably P2Y-receptor-mediated effect on the smooth muscle. All motor effects of ATP are inhibited by the antagonist PPADS.
三磷酸腺苷（ATP）可能是胃肠道中的一种重要神经递质。本研究检测了外源性ATP对豚鼠离体回肠纵向肌条制剂的运动效应以及药物对ATP诱导反应的影响。高微摩尔浓度的ATP引起两种类型的收缩，一种是相位性的、胆碱能反应，另一种是强直性的、对河豚毒素耐药的收缩。六甲铵（5×10⁻⁵ M）可降低相位性收缩，但辣椒素快速耐受或对α,β-亚甲基ATP的快速耐受对其无影响。强直性反应对阿托品、六甲铵、辣椒素、ω-芋螺毒素GVIA或用α,β-亚甲基ATP预处理均有抗性。两种类型的ATP诱导收缩均被P2嘌呤受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸（PPADS，分别为3×10⁻⁶和3×10⁻⁵ M）减弱或消除。在预先收缩且经阿托品处理的回肠中，ATP（10⁻⁶ - 10⁻⁴ M）引起对胍乙啶耐药的舒张。这种反应不受河豚毒素、ω-芋螺毒素GVIA或NG-硝基-L-精氨酸的影响，但被蜂毒明肽（10⁻⁷ M）消除，并被PPADS（3×10⁻⁵ M）或活性蓝2（10⁻⁵ M）以可克服的方式抑制。观察到ATP（10⁻⁵ - 10⁻⁴ M）的舒张作用存在高度快速耐受。高浓度（3×10⁻⁴ M）的PPADS未能影响回肠对外源性乙酰胆碱或组胺的收缩。结论是，除了在豚鼠回肠中的直接收缩作用外，ATP还可激活（部分为节前）胆碱能神经元，其作用机制与α,β-亚甲基ATP的机制有很大不同。ATP还通过对平滑肌的直接、可能由P2Y受体介导的作用引起舒张。ATP的所有运动效应均被拮抗剂PPADS抑制。
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