Submitted on August 31, 2007
Accepted on January 9, 2008
Characterization of noradrenergic transmission at the Dorsal Motor Nucleus of the Vagus involved in reflex control of fundus tone
Melissa A. Herman1, Mark Niedringhaus2, Alisa Alayan3, Joseph G. Verbalis4, Niaz Sahibzada5, and Richard A. Gillis5*
1 both authors contributed equally to this work, United States; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States
2 both authors contributed equally to this work, United States; Pharmacology, Georgetown University Medical Center, Washington, District of Columbia, United States
3 Pharmacology, Georgetown University Medical Center, Washington, District of Columbia, United States
4 Endocrinology and Metabolism, Georgetown University Medical Center, Washington, District of Columbia, United States
5 Dept. of Pharmacology, Georgetown University Medical Center, Washington, District of Columbia, United States
* To whom correspondence should be addressed. E-mail: gillisr{at}georgetown.edu.
Quantitative analysis of innervation to Dorsal Motor Nucleus of the Vagus (DMV) fundus-projecting neurons indicates that approximately 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 vago-vagal 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 minute interval between distensions. Bilateral cervical vagotomy and/or pretreatment with intravenous atropine methylbromide prevented the reflex-induced fundus relaxation. In contrast, intravenous L-NAME had no effect. Bilateral microinjection of alpha 2-adrenoreceptor antagonists (yohimbine and RS-79948) into the DMV also prevented the response. Prior to 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.
