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Am J Physiol Regul Integr Comp Physiol 294: R720-R729, 2008. First published January 16, 2008; doi:10.1152/ajpregu.00630.2007
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Characterization of noradrenergic transmission at the dorsal motor nucleus of the vagus involved in reflex control of fundus tone

Melissa A. Herman,1,* Mark Niedringhaus,2,* Alisa Alayan,2 Joseph G. Verbalis,3 Niaz Sahibzada,2 and Richard A. Gillis2

1Interdisciplinary Program in Neuroscience, 2Departments of Pharmacology and 3Medicine, Georgetown University Medical Center, Washington, District of Columbia

Submitted 31 August 2007 ; accepted in final form 9 January 2008

Quantitative analysis of innervation to dorsal motor nucleus of the vagus (DMV) fundus-projecting neurons indicates that ~17% of input neurons are noradrenergic. To determine whether this small percentage of neurons innervating DMV output to the stomach is physiologically relevant, we evaluated the role of norepinephrine at the DMV in mediating a vagovagal reflex controlling the fundus. A strain gauge was sutured onto the fundus of isoflurane-anesthetized rats to monitor changes in tone evoked by esophageal distension (ED). ED produced a decrease in fundus tone of 0.31 ± 0.02 g (P < 0.05), which could be reproduced after a 30-min interval between distensions. Bilateral cervical vagotomy and/or pretreatment with intravenous atropine methylbromide prevented the reflex-induced fundus relaxation. In contrast, intravenous NG-nitro-L-arginine methyl ester had no effect. Bilateral microinjection of {alpha}2-adrenoreceptor antagonists (yohimbine and RS-79948) into the DMV also prevented the response. Before microinjection of {alpha}2-adrenoreceptor antagonists, ED decreased fundus tone by 0.33 ± 0.05 g (P < 0.05). After antagonist microinjection, ED decreased fundus tone by only 0.05 ± 0.06 g (P > 0.05). Bilateral microinjection of prazosin into the DMV had no effect on the response. Microinjection of norepinephrine into the DMV mimicked the effect of ED and was also prevented by prior microinjection of an {alpha}2-adrenoreceptor antagonist. Our results indicate that noradrenergic innervation of DMV fundus-projecting neurons is physiologically important and suggest that norepinephrine released at the DMV acts on {alpha}2-adrenoreceptors to inhibit activity in a cholinergic-cholinergic excitatory pathway to the fundus.

gastric tone; norepinephrine; rat



Address for reprint requests and other correspondence: R. A. Gillis, Dept. of Pharmacology, Georgetown Univ. Medical Center, 3900 Reservoir Rd. NW, Washington, DC 20007 (e-mail: gillisr{at}georgetown.edu)







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