Characterization of noradrenergic transmission at the dorsal motor nucleus of the vagus involved in reflex control of fundus tone.
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 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 N(G)-nitro-L-arginine methyl ester had no effect. Bilateral microinjection of alpha2-adrenoreceptor antagonists (yohimbine and RS-79948) into the DMV also prevented the response. Before microinjection of alpha2-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 alpha2-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 alpha2-adrenoreceptors to inhibit activity in a cholinergic-cholinergic excitatory pathway to the fundus.
Herman
Melissa A
MA
Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3900 Reservoir Rd. NW, Washington, DC 20007, USA.
Niedringhaus
Mark
M
Alayan
Alisa
A
Verbalis
Joseph G
JG
Sahibzada
Niaz
N
Gillis
Richard A
RA
D018674:Adrenergic Antagonists / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D004106:Dilatation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004947:Esophagus / Q000502:physiology; D005748:Gastric Fundus; D008297:Male; D008845:Microinjections; D009046:Motor Neurons / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*
D018674:Adrenergic Antagonists; D058646:Adrenergic alpha-1 Receptor Agonists; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D001285:Atropine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine