Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine.
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.
Ferreira
Manuel
M
Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Rd., NW, Washington, Distric of Columbia 20007, USA.
Sahibzada
Niaz
N
Shi
Min
M
Niedringhaus
Mark
M
Wester
Matthew R
MR
Jones
Allison R
AR
Verbalis
Joseph G
JG
Gillis
Richard A
RA
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
D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D009538:Nicotine; D019331:NG-Nitroarginine Methyl Ester