长期暴露于α,β-亚甲基ATP对鸡直肠非肾上腺素能、非胆碱能兴奋性传递的影响。

Effects of prolonged exposure to alpha,beta-methylene ATP on non-adrenergic, non-cholinergic excitatory transmission in the rectum of the chicken.

作者信息

Komori S, Kwon S C, Ohashi H

机构信息

Department of Veterinary Science, Faculty of Agriculture, Gifu University, Japan.

出版信息

Br J Pharmacol. 1988 May;94(1):9-18. doi: 10.1111/j.1476-5381.1988.tb11494.x.

DOI:10.1111/j.1476-5381.1988.tb11494.x

PMID:2840995

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1853943/

Abstract

Effects of prolonged exposure to alpha,beta-methylene ATP (alpha,beta-Me ATP) on contractions and excitatory junction potentials (e.j.ps) evoked by non-adrenergic, non-cholinergic (NANC) excitatory nerve stimulation have been investigated in the chicken isolated rectum and longitudinal muscle strip from chicken rectum pretreated with atropine (0.5 microM), methysergide (2 microM) and pyrilamine (3 microM). 2. Alpha,beta-Me ATP (20 nM-4 microM) caused a rapid rise in tension of the longitudinal muscle of the isolated rectum preparation which returned to the baseline levels after a few minutes. The magnitude of the contractile response to NANC nerve stimulation was reduced after exposure to the drug. The inhibitory effect was related to the drug concentration; at 4 microM the nerve-mediated contraction was abolished and frequently converted to a relaxation. 3. Adenosine 5'-triphosphate (ATP, 100 microM), bovine neurotensin (2.5 nM) and K+-rich solutions (30 nM and 60 nM) all produced a transient contraction of the isolated rectum preparation. The exposure to alpha,beta-Me ATP (0.2 and 4 microM) also rendered the preparation less sensitive to these stimulant substances. 4. Alpha,beta-Me ATP (0.2 and 4 microM) caused a membrane depolarization in cells of the longitudinal muscle strip. The depolarization reached a peak within 2-3 min after application and then decayed to a steady level that was still more positive than the baseline level. The electrotonic potentials were reduced in amplitude to 44 +/- 8% (n = 7) of the normal amplitude if measured at the peak depolarization produced with 0.2 microM alpha,beta-Me ATP, and to 62 +/- 10% (n = 7) if measured at the steady-state depolarization. With 4 microM, the corresponding percentages were 33 +/- 7% (n = 8) and 55 +/- 7% (n = 8), indicating a decrease in membrane resistance. 5. The e.j.ps in response to field stimulation of the intramural nerves and Remak's nerve stimulation were decreased in amplitude and duration during exposure to alpha,beta-Me ATP (0.2 and 4 microM). 6. The smooth muscle cells regained normal membrane resistance and sensitivity to ATP on washout of alpha,beta-Me ATP (4 microM) more rapidly than the responses to NANC nerve stimulation. 7. It can be argued from the results that the suppression by alpha,beta-Me ATP of the contraction and e.j.p. evoked by NANC nerve stimulation in the chicken rectum, unlike the mammalian preparation described previously, is due mainly to a change in the electrical properties of the membrane of the smooth muscle cells, rather than being due, or only partly due, to desensitization of the purine receptor.

摘要

本研究在经阿托品（0.5微摩尔）、麦角新碱（2微摩尔）和吡苄明（3微摩尔）预处理的鸡离体直肠及直肠纵肌条中，探究了长时间暴露于α,β-亚甲基三磷酸腺苷（α,β-Me ATP）对非肾上腺素能、非胆碱能（NANC）兴奋性神经刺激所诱发的收缩和兴奋性接头电位（e.j.ps）的影响。2. α,β-Me ATP（20纳摩尔至4微摩尔）可使离体直肠纵肌条的张力迅速升高，几分钟后恢复至基线水平。暴露于该药物后，对NANC神经刺激的收缩反应幅度降低。抑制作用与药物浓度相关；在4微摩尔时，神经介导的收缩被消除，且常转变为舒张。3. 三磷酸腺苷（ATP，100微摩尔）、牛神经降压素（2.5纳摩尔）和富钾溶液（30纳摩尔和60纳摩尔）均可使离体直肠纵肌条产生短暂收缩。暴露于α,β-Me ATP（0.2和4微摩尔）也使该肌条对这些刺激物质的敏感性降低。4. α,β-Me ATP（0.2和4微摩尔）可使纵肌条细胞发生膜去极化。去极化在施加药物后2至3分钟内达到峰值，然后衰减至仍高于基线水平的稳定状态。若在0.2微摩尔α,β-Me ATP产生的去极化峰值处测量，电紧张电位幅度降至正常幅度的44±8%（n = 7）；若在稳态去极化时测量，则降至62±10%（n = 7）。使用4微摩尔时，相应百分比分别为33±7%（n = 8）和55±7%（n = 8），表明膜电阻降低。5. 在暴露于α,β-Me ATP（0.2和4微摩尔）期间，对壁内神经的场刺激和雷马克神经刺激所产生的e.j.ps的幅度和持续时间均减小。6. 冲洗掉α,β-Me ATP（4微摩尔）后，平滑肌细胞恢复正常膜电阻和对ATP的敏感性的速度，比恢复对NANC神经刺激的反应速度更快。7. 从结果可以推断，与先前描述的哺乳动物标本不同，α,β-Me ATP对鸡直肠中NANC神经刺激所诱发的收缩和e.j.p.的抑制作用，主要是由于平滑肌细胞膜电特性的改变，而非主要由于嘌呤受体脱敏或仅部分由于嘌呤受体脱敏所致。