title: Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine.
abstract: The purpose of this study was to activate a vagovagal reflex by using esophageal distension and nicotine and test whether hindbrain nitric oxide and norepinephrine are involved in this reflex function. We used double-labeling immunocytochemical methods to determine whether esophageal distension (and nicotine) activates c-Fos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarii (NTS). We also studied c-Fos expression in the dorsal motor nucleus of the vagus (DMV) neurons projecting to the periphery. Esophageal distension caused 19.7 +/- 2.3% of the noradrenergic NTS neurons located 0.60 mm rostral to the calamus scriptorius (CS) to be activated but had little effect on c-Fos in DMV neurons. Intravenous administration of nicotine caused 19.7 +/- 4.2% of the noradrenergic NTS neurons 0.90 mm rostral to CS to be activated and, as reported previously, had no effect on c-Fos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central mediators of esophageal distension-induced decrease in intragastric pressure (balloon recording), N(G)-nitro-L-arginine methyl ester microinjected into the NTS (n = 5), but not into the DMV, blocked the vagovagal reflex. Conversely, alpha2-adrenergic blockers microinjected into the DMV (n = 7), but not into the NTS, blocked the vagovagal reflex. These data, in combination with our earlier pharmacological microinjection data with nicotine, indicate that both esophageal distension and nicotine produce nitric oxide in the NTS, which then activates noradrenergic neurons that terminate on and inhibit DMV neurons.
authors.affiliation: Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Rd., NW, Washington, Distric of Columbia 20007, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferreira
authors.forename: Niaz
authors.initials: N
authors.lastname: Sahibzada
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Mark
authors.initials: M
authors.lastname: Niedringhaus
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Wester
authors.forename: Allison R
authors.initials: AR
authors.lastname: Jones
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gillis
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004947:Esophagus / Q000294:innervation* / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012249:Rhombencephalon / Q000737:chemistry*; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D009538:Nicotine; D019331:NG-Nitroarginine Methyl Ester