Bayer S, Crenner F, Aunis D, Angel F
INSERM Unité 338. Groupe de Neurogastroentérologie. Pavillon Poincaré. Hôpital Civil. 67000 Strasbourg, France.
Life Sci. 2002 Jul 12;71(8):911-25. doi: 10.1016/s0024-3205(02)01771-x.
GABAergic regulation of intestinal motility through the modulation of non-adrenergic non-cholinergic (NANC) neurons remains poorly understood especially in rat colon where very few studies have been undertaken. Therefore, the effects of GABA on circular preparations of rat distal colon were investigated using classical organ bath chambers to record spontaneous mechanical activities (SMA). SMA was characterized by the occurrence of rhythmic phasic contractions (type-I) or by spontaneously occurring large contractions superimposed on small rhythmic contractions (type-II). In the presence of atropine and guanethidine (NANC conditions), these large contractions were inhibited by bicuculline, a GABA(A)-receptor antagonist as well as by TTX, L-NAME and apamin together, or L 732-138, a NK1-receptor antagonist. In NANC conditions, GABA induced a transient monophasic relaxation or a biphasic effect characterized by a relaxation followed by a tonic contraction in both type-I and -II preparations. Both the inhibitory and excitatory effects of GABA were blocked by TTX and L-NAME + apamin; the GABA-induced contraction was also sensitive to L 732-138. The responses to GABA were mimicked by the GABA(A)-receptor agonist, muscimol, whereas baclofen and CACA, respectively GABA(B) and GABA(C)-receptors agonists showed no effect. These results demonstrated that only GABA(A)-receptors seem to be involved in the regulation of SMA in rat distal colon in NANC conditions. Release of NANC inhibitory transmitter (NO and probably ATP) and NANC excitatory transmitter (maybe substance P) might be involved.
γ-氨基丁酸（GABA）通过调节非肾上腺素能非胆碱能（NANC）神经元对肠道运动的调节作用仍知之甚少，尤其是在大鼠结肠中，相关研究极少。因此，本研究使用经典的器官浴槽记录大鼠远端结肠环行肌条的自发机械活动（SMA），以探讨GABA的作用。SMA表现为有节律的相性收缩（I型）或自发出现的大收缩叠加在小的节律性收缩之上（II型）。在阿托品和胍乙啶存在的情况下（NANC条件），这些大收缩被GABA(A)受体拮抗剂荷包牡丹碱以及TTX、L-NAME和蜂毒明肽共同作用所抑制，或者被NK1受体拮抗剂L 732-138所抑制。在NANC条件下，GABA在I型和II型肌条中均诱导出短暂的单相松弛或双相效应，其特征为先松弛后出现强直性收缩。GABA的抑制和兴奋作用均被TTX以及L-NAME + 蜂毒明肽所阻断；GABA诱导的收缩也对L 732-138敏感。GABA(A)受体激动剂蝇蕈醇可模拟对GABA的反应，而GABA(B)和GABA(C)受体激动剂巴氯芬和CACA则无作用。这些结果表明，在NANC条件下，大鼠远端结肠中似乎只有GABA(A)受体参与SMA的调节。可能涉及NANC抑制性递质（一氧化氮和可能的三磷酸腺苷）和NANC兴奋性递质（可能是P物质）的释放。
