Maggi C A, Manzini S, Meli A
J Auton Pharmacol. 1984 Jun;4(2):77-85. doi: 10.1111/j.1474-8673.1984.tb00084.x.
GABA produced rapid and transient relaxation of rat duodenum. Homotaurine (3-aminopropansulphonic acid) but not (+/-)-baclofen had a GABA-like effect. GABA-induced relaxation was almost completely inhibited by tetrodotoxin but was unaffected by atropine. Cross desensitization developed between GABA and homotaurine but not between GABA and (+/-)-baclofen. The concentration response curve to the relaxant effects of GABA was shifted to the right by both bicuculline and picrotoxin. However maximal relaxation was still produced by GABA in the presence of bicuculline but not in the presence of picrotoxin. GABA-induced relaxation was not affected by prazosin, yohimbine, propranolol or reserpine pretreatment. Field stimulation (0.1 Hz) of rat isolated duodenum in the presence of atropine and guanethidine produced relaxation similar to that produced by GABA. The ganglionic stimulant DMPP produced a similar effect. Neither Met-enkephalin, noradrenaline, 5-HT, histamine, VIP or arachidonic acid could be held responsible for GABA-induced neurogenic relaxation of rat duodenum. ATP produced relaxations which closely mimicked those produced by either GABA or field stimulation. Exposure to ATP desensitized responses to both GABA and field stimulation to about the same extent. ATP, GABA and field stimulation-induced relaxation was unaffected by either theophylline or indomethacin, but was significantly and selectively antagonized by apamin. In conclusion, GABA-induced relaxation of rat isolated duodenum is largely dependent upon activation of intra-mural nonadrenergic-noncholinergic neurones. The GABA receptor involved appears to be of the GABAA subtype. Circumstantial evidence is provided indicating that ATP might be the endogenous substance released by GABA.
γ-氨基丁酸（GABA）可使大鼠十二指肠迅速产生短暂的松弛。高牛磺酸（3-氨基丙烷磺酸）具有类似GABA的作用，而（±）-巴氯芬则没有。河豚毒素几乎完全抑制了GABA诱导的松弛，但阿托品对其没有影响。GABA和高牛磺酸之间出现了交叉脱敏现象，而GABA和（±）-巴氯芬之间则没有。荷包牡丹碱和印防己毒素均使GABA松弛效应的浓度-反应曲线右移。然而，在荷包牡丹碱存在的情况下，GABA仍能产生最大松弛效应，而在印防己毒素存在时则不能。哌唑嗪、育亨宾、普萘洛尔或利血平预处理对GABA诱导的松弛没有影响。在阿托品和胍乙啶存在的情况下，对大鼠离体十二指肠进行场刺激（0.1Hz）产生的松弛与GABA产生的松弛相似。神经节兴奋剂二甲基苯基哌嗪（DMPP）也产生了类似的效果。甲硫氨酸脑啡肽、去甲肾上腺素、5-羟色胺、组胺、血管活性肠肽或花生四烯酸均不能引起大鼠十二指肠GABA诱导的神经源性松弛。三磷酸腺苷（ATP）产生的松驰与GABA或场刺激产生的松驰极为相似。暴露于ATP使对GABA和场刺激的反应脱敏程度大致相同。茶碱或吲哚美辛对ATP、GABA和场刺激诱导的松弛均无影响，但蜂毒明肽能显著且选择性地拮抗它们。总之，GABA诱导的大鼠离体十二指肠松弛很大程度上依赖于肠壁内非肾上腺素能-非胆碱能神经元的激活。所涉及的GABA受体似乎是GABAA亚型。有间接证据表明ATP可能是GABA释放的内源性物质。
