GABAA受体功能在豚鼠回肠蠕动活动中的作用：与荷包牡丹碱、SR 95531和印防己毒素的比较研究

The role of GABAA receptor function in peristaltic activity of the guinea-pig ileum: a comparative study with bicuculline, SR 95531 and picrotoxinin.

Tonini M, De Petris G, Onori L, Manzo L, Rizzi C A, Crema A

Department of Internal Medicine and Therapeutics, University of Pavia, Italy.

Br J Pharmacol. 1989 Jun;97(2):556-62. doi: 10.1111/j.1476-5381.1989.tb11985.x.

Abstract

The peristaltic activity of the guinea-pig ileum was studied in the absence and in the presence of the blockade of GABAA receptors. 2. Bicuculline (1-30 microM), improved at the highest concentrations the efficiency of peristalsis by enhancing the frequency of propulsive contractions and the amount of fluid ejected per unit of time. 3. Neither SR 95531 (0.3-10 microM), a novel GABAA receptor antagonist, which competitively antagonized 3-aminopropane sulphonic acid induced contractions in myenteric plexus-longitudinal muscle preparations (pA2 value: 6.47), nor picrotoxinin (1-30 microM) modified peristaltic parameters or influenced the potentiating effect of bicuculline on peristaltic activity. 4. In myenteric plexus-longitudinal muscle preparations, bicuculline (1-30 microM) enhanced the amplitude of electrically-induced cholinergic contractions without modifying submaximal contractions to applied acetylcholine. SR 95531 and picrotoxinin had no effect on twitch amplitude. In the presence of each of these compounds, bicuculline retained its potentiating effect. 5. The results obtained with SR 95531 and picrotoxinin question the view that GABAA receptors may exert a critical role in intestinal propulsion by modulating the activity of nerve pathways subserving peristalsis. Bicuculline potentiates the peristaltic activity of the ileum probably via a facilitatory effect on enteric cholinergic transmission that is independent of GABAA receptor blockade.

摘要

在不存在和存在GABAA受体阻断的情况下，研究了豚鼠回肠的蠕动活动。2. 荷包牡丹碱（1 - 30微摩尔）在最高浓度时通过提高推进性收缩的频率和单位时间内排出的液体量来改善蠕动效率。3. 新型GABAA受体拮抗剂SR 95531（0.3 - 10微摩尔），它能竞争性拮抗3 - 氨基丙烷磺酸诱导的肠肌丛 - 纵肌标本收缩（pA2值：6.47），以及印防己毒素（1 - 30微摩尔），均未改变蠕动参数，也未影响荷包牡丹碱对蠕动活动的增强作用。4. 在肠肌丛 - 纵肌标本中，荷包牡丹碱（1 - 30微摩尔）增强了电诱导的胆碱能收缩的幅度，而不改变对应用乙酰胆碱的次最大收缩。SR 95531和印防己毒素对抽搐幅度无影响。在这些化合物各自存在的情况下，荷包牡丹碱保留其增强作用。5. 用SR 95531和印防己毒素获得的结果对GABAA受体可能通过调节参与蠕动的神经通路活动在肠道推进中发挥关键作用这一观点提出了质疑。荷包牡丹碱可能通过对肠胆碱能传递的促进作用来增强回肠的蠕动活动，而这种作用独立于GABAA受体阻断。