Tonic GABA A receptor-mediated neurotransmission in the dorsal vagal complex regulates intestinal motility in rats

Abstract

Vagal motor outflow from the dorsal vagal complex is important in the regulation of intestinal motility. The aim of our study was to test the hypothesis that within the dorsal vagal complex, tonic GABA A-receptor mediated neurotransmission modulates intestinal motility. The GABA A receptor antagonist, bicuculline (methiodide), was microinjected into the dorsal vagal complex, and the effects on small intestinal and colonic motility were investigated. Rats were anesthetized and the mean arterial pressure and heart rate were monitored. Jejunal and colonic motility were measured manometrically, and motility indices were calculated manually. Bicuculline at concentrations of 0.25 or 0.5 mM in 30 nl was microinjected bilaterally into the dorsal vagal complex through stereotaxically placed micropipettes. The injection sites were confirmed histologically using the dye Alcian Blue. Bicuculline (0.5 mM) inhibited spontaneous jejunal motility by 76.3%, colonic motility by 51.7%, mean arterial pressure by 23.3% and heart rate by 27.6%. The lower concentration of bicuculline (0.25 mM) showed no inhibitory effects on intestinal motility but decreased mean arterial blood pressure by 24.1% and heart rate by 13.6%. Bilateral cervical vagotomy attenuated the bicuculline (0.5 mM)-induced inhibition of spontaneous jejunal motility, whereas the bicuculline effect on colonic motility was unaffected. The results of this study show that GABA A receptor-mediated neurotransmission in the dorsal vagal complex is involved in autonomic integration of motility of the small intestine and colon. Furthermore, our results indicate that the dorsal vagal complex regulation of jejunal motility involves vagal outflow, whereas vagal pathways do not participate in the bicuculline-induced inhibition of colonic motility.