TY - JOUR
T1 - Tonic GABA(A) receptor-mediated neurotransmission in the dorsal vagal complex regulates intestinal motility in rats
AU - Greenwood-Van Meerveld, Beverley
AU - Barron, Kirk W.
N1 - Funding Information:
The authors would like to thank Denise Steig and Fadi Nasr for their excellent technical support, and Dr. Malcolm Robinson for his helpful comments on the manuscript preparation. Part of this work has previously been reported in abstract form at the Annual Meeting of Experimental Biology (Washington, DC, 1996) and the American Gasteroenterological Association (Washington, DC, 1997). The work was supported in part by the Presbyterian Health Foundation and the American Heart Association, Oklahoma Affiliate.
PY - 1998/4/10
Y1 - 1998/4/10
N2 - 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.
AB - 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.
KW - Bicuculline
KW - Brainstem
KW - Colon
KW - GABA (γ-aminobutyric acid)
KW - GABA(A) receptor
KW - Jejunum
KW - Motility
KW - Vagus
UR - http://www.scopus.com/inward/record.url?scp=0344333479&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(98)00071-5
DO - 10.1016/S0014-2999(98)00071-5
M3 - Article
C2 - 9652360
AN - SCOPUS:0344333479
SN - 0014-2999
VL - 346
SP - 197
EP - 202
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -