Maggi C A, Santicioli P, Meli A
J Auton Pharmacol. 1985 Mar;5(1):55-64. doi: 10.1111/j.1474-8673.1985.tb00565.x.
The effects of various GABAA and GABAB receptor agonists and antagonists on electrically induced contractions of detrusor strips from guinea-pig urinary bladder dome were investigated by using both supra and submaximal parameters of stimulation. In supramaximally stimulated preparations GABA (1 mM) inhibited amplitude of contractions. This effect was mimicked, to a lesser degree, by the selective GABAB receptor agonist, (+/-)-baclofen (0.1 mM). Exposure to (+/-)-baclofen reduced markedly the effects of a subsequent challenge with GABA. The GABAA receptor agonists, muscimol (0.3 mM) and homotaurine (1 mM), produced a slight inhibition of contractions and reduced the effects of a subsequent challenge with GABA. The selective GABAA receptor antagonist, picrotoxin (0.1 mM), had a slight, but significant, antagonistic effect toward GABA, but had no effect against (+/-)-baclofen. GABA inhibition of supramaximally stimulated contractions was partly reduced by previous exposure to atropine (3 microM) or to the putative P2-purinoreceptor antagonist, reactive blue 2 (0.3 mM) as well as by desensitization of P2-purinoreceptors produced by the stable ATP analogue beta-gamma-methylene ATP (APPCP). GABA inhibition was unaffected by phentolamine (0.2 microM), propranolol (0.3 microM) or hexamethonium (10 microM). The inhibition produced by atropine plus reactive blue 2 or APPCP desensitization was additive or more than additive. In submaximally stimulated preparations GABA (0.01-1 mM) produced a transient, concentration related enhancement of amplitude of contractions. This effect was mimicked by either muscimol (0.3 mM) or homotaurine (1 mM) but not by (+/-)-baclofen (0.1 mM). A cross desensitization could be observed between the effects of muscimol or homotaurine on one hand and GABA on the other, but not between (+/-)-baclofen and GABA. Picrotoxin (0.03-0.1 mM) produced a concentration dependent antagonism of a noncompetitive type against the excitatory effect of GABA in submaximally stimulated preparations. Previous exposure to either atropine (3 microM), phentolamine (0.2 microM) or hexamethonium (10 microM) failed to affect GABA induced enhancement of submaximally stimulated contractions. On the other hand the effects of GABA were reduced by reactive blue 2 (0.1-0.9 mM) or by desensitization of P2-purinoreceptors. In preparations exposed to tetrodotoxin (TTX, 0.3 microM), field stimulation induced contractions are attributable to a direct excitation of smooth muscle cells. Under these conditions GABA (1 mM) was ineffective, indicating that, in the absence of TTX, it affects the excitability of neural elements in the bladder wall.(ABSTRACT TRUNCATED AT 400 WORDS)
运用超最大和次最大刺激参数，研究了多种γ-氨基丁酸A（GABAA）和γ-氨基丁酸B（GABAB）受体激动剂及拮抗剂对豚鼠膀胱顶部逼尿肌条电诱发收缩的影响。在超最大刺激的标本中，γ-氨基丁酸（GABA，1 mM）抑制收缩幅度。选择性GABAB受体激动剂（±）-巴氯芬（0.1 mM）在较小程度上模拟了这种效应。暴露于（±）-巴氯芬显著降低了随后用GABA刺激的效应。GABAA受体激动剂蝇蕈醇（0.3 mM）和高牛磺酸（1 mM）对收缩有轻微抑制作用，并降低了随后用GABA刺激的效应。选择性GABAA受体拮抗剂印防己毒素（0.1 mM）对GABA有轻微但显著的拮抗作用，但对（±）-巴氯芬无作用。预先暴露于阿托品（3 μM）或推定的P2嘌呤受体拮抗剂反应性蓝2（0.3 mM）以及由稳定的ATP类似物β-γ-亚甲基ATP（APPCP）使P2嘌呤受体脱敏，均可部分降低GABA对超最大刺激收缩的抑制作用。GABA的抑制作用不受酚妥拉明（0.2 μM）、普萘洛尔（0.3 μM）或六甲铵（10 μM）的影响。阿托品加反应性蓝2或APPCP脱敏所产生的抑制作用是相加的或超过相加的。在次最大刺激的标本中，GABA（0.01 - 1 mM）产生与浓度相关的短暂收缩幅度增强。这种效应可被蝇蕈醇（0.3 mM）或高牛磺酸（1 mM）模拟，但不能被（±）-巴氯芬（0.1 mM）模拟。在蝇蕈醇或高牛磺酸与GABA之间可观察到交叉脱敏，但在（±）-巴氯芬与GABA之间未观察到。印防己毒素（0.03 - 0.1 mM）对次最大刺激标本中GABA的兴奋作用产生非竞争性的浓度依赖性拮抗。预先暴露于阿托品（3 μM）、酚妥拉明（0.2 μM）或六甲铵（10 μM）均未能影响GABA诱导的次最大刺激收缩增强。另一方面，反应性蓝2（0.1 - 0.9 mM）或P2嘌呤受体脱敏可降低GABA的作用。在暴露于河豚毒素（TTX，0.3 μM）的标本中，场刺激诱发的收缩归因于平滑肌细胞的直接兴奋。在这些条件下，GABA（1 mM）无效，表明在无TTX时，它影响膀胱壁神经元的兴奋性。（摘要截选至400字）
