[automatically translated] The gamma-amino butyric acid (GABA) is widely recognized as a major inhibitory neurotransmitter in the central nervous system of mammals. However, several lines of evidence suggest its action at the level of the enteric nervous system (or "little brain"), deputy section of the peripheral nervous system to control the functions of the gastrointestinal tract (GI). Since, to date, the effects of GABA are still unclear and seem to depend on the portion of the GI tract in question or from animal model examined, the aim of this work was to study the effect of GABA on the circular muscle contractility the distal colon in the mouse model. To this end we were used: i) an isolated organ bath for vertical, in order to record, into the strip muscle, the mechanical spontaneous activity and contractile responses evoked by electrical stimulation of cholinergic neurons enteric ii) a modified Trendelenburg system, through which the gradual distension of the bowel wall induces, by reflex, the appearance of rhythmic contractions able to propagate in the direction aborale , identified as peristaltic waves. The GABA up to the dose of 1 mM did not significantly affect the spontaneous mechanical activity of the muscle strip, but on the contrary induced different effects on evoked responses, in relation to the concentration used. At low concentrations (10-100 mM) GABA caused a significant increase in neuronal cholinergic contraction amplitude and frequency and amplitude of peristaltic contractions. The exciters effects were antagonized by pretreatment of the samples with the selective GABAA receptor antagonist (bicuculline), which in itself reduced cholinergic neural contractions and peristaltic activity, and mimicked by muscimol, a selective agonist of the GABAA receptor. In contrast, high concentrations of GABA (0.5-1 mM) caused an inhibitory effect on neural cholinergic contractions and peristaltic activity. These inhibitory effects were antagonized by pretreatment of samples with phaclofen, selective antagonist of the GABA B receptor, which in itself showed no significant effects mechanical activity, and mimed by baclofen, agonist of GABA B receptors. Finally, the administration of the agonist and antagonist GABAC receptors showed no significant effect on the responses induced by the GABA. In conclusion, our data suggest a role for GABA as a neuromodulator of acetylcholine release from enteric neurons in the mouse distal colon through a different activation of GABAA and GABAB receptors. The GABAA receptors appear active tonically being recruited at low GABA concentrations, and increase the release of acetylcholine by enteric neurons. The GABAB receptors, recruited to high concentrations of GABA, would induce the opposite effects, reducing the release of acetylcholine. These effects are reflected on gastrointestinal function, modulating the motor pattern peristaltic and consequently the propulsion of the luminal content along the distal portion of the GI tract.
|Number of pages||2|
|Publication status||Published - 2013|