Smid S D, Young R L, Cooper N J, Blackshaw L A
Nerve-Gut Research Laboratory, Level 1 Hanson Centre, Adelaide SA 5000, Australia.
Am J Physiol Gastrointest Liver Physiol. 2001 Dec;281(6):G1494-501. doi: 10.1152/ajpgi.2001.281.6.G1494.
GABA(B)-receptor (GABA(B)R) agonists reduce transient lower esophageal sphincter relaxation (TLESR) and reflux episodes through an action on vagal pathways. In this study, we determined whether GABA(B)R are expressed on vagal afferent neurones and whether they modulate distension-evoked discharge of vagal afferents in the isolated stomach. Vagal mehanoreceptor activity was recorded following distensions of the isolated ferret proximal stomach before and after perfusion with the GABA(B)R-selective agonists baclofen and 3-aminopropylphosphinic acid (3-APPiA). Retrograde labeling and immunohistochemistry were used to identify GABA(B)R located on vagal afferent neurones in the nodose ganglia. Vagal afferent fibers responded to isovolumetric gastric distension with an increase in discharge. The GABA(B)-receptor agonists baclofen (5 x 10(-5) M) and 3-APPiA (10(-6) to 10(-5) M) but not muscimol (GABA(A)-selective agonist: 1.3 x 10(-5) M) significantly decreased afferent distension-response curves. The effect of baclofen (5 x 10(-5) M) was reversed by the GABA(B)-receptor antagonist CGP 62349 (10(-5) M). Over 93% of retrogradely labeled gastric vagal afferents in the nodose ganglia expressed immunoreactivity for the GABA(B)R. GABA(B)R expressed on vagal afferent fibers directly inhibit gastric mechanosensory activity. This is likely a contributing mechanism to the efficacy of GABA(B)-receptor agonists in reducing TLESR and reflux episodes in vivo.
γ-氨基丁酸B型受体（GABA(B)R）激动剂通过作用于迷走神经通路来减少一过性下食管括约肌松弛（TLESR）和反流发作。在本研究中，我们确定了GABA(B)R是否在迷走神经传入神经元上表达，以及它们是否调节离体胃中牵张诱发的迷走神经传入放电。在用GABA(B)R选择性激动剂巴氯芬和3-氨基丙基次膦酸（3-APPiA）灌注前后，记录了离体雪貂近端胃扩张后的迷走机械感受器活性。采用逆行标记和免疫组织化学方法鉴定结节神经节中位于迷走神经传入神经元上的GABA(B)R。迷走神经传入纤维对等容性胃扩张的反应是放电增加。GABA(B)R激动剂巴氯芬（5×10⁻⁵ M）和3-APPiA（10⁻⁶至10⁻⁵ M），而非蝇蕈醇（GABA(A)选择性激动剂：1.3×10⁻⁵ M），显著降低了传入扩张反应曲线。GABA(B)受体拮抗剂CGP 62349（10⁻⁵ M）可逆转巴氯芬（5×10⁻⁵ M）的作用。结节神经节中超过93%的逆行标记胃迷走神经传入纤维对GABA(B)R呈免疫反应阳性。迷走神经传入纤维上表达的GABA(B)R直接抑制胃机械感觉活动。这可能是GABA(B)R激动剂在体内减少TLESR和反流发作疗效的一个促成机制。
