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Am J Physiol Regul Integr Comp Physiol (July 28, 2005). doi:10.1152/ajpregu.00003.2005
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Submitted on January 6, 2005
Accepted on July 19, 2005

Hindbrain Chemical Mediators of Reflex-Induced Inhibition of Gastric Tone Produced by Esophageal Distension and I.V. Nicotine

Manuel Ferreira, Jr.1, Niaz Sahibzada1, Min Shi2, Mark Niedringhaus1, Matthew R Wester1, Allison R Jones1, Joseph G Verbalis2, and Richard A Gillis1*

1 Pharmacology, Georgetown University Medical Center, Washington, DC, USA
2 Medicine (Endocrinology), Georgetown University Medical Center, Washington, DC, USA

* To whom correspondence should be addressed. E-mail: gillisr{at}georgetown.edu.

The purpose of this study was to activate a vago-vagal reflex 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 cFos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarius (NTS). We also studied cFos 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 scriptorus (CS) to be activated, but had little effect on cFos 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 cFos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central mediators of esophageal distension-induced decrease in intragastric pressure (balloon recording), L-NAME microinjected into the NTS (n=5), but not into the DMV, blocked the vago-vagal reflex. Conversely, {alpha}2 adrenergic blockers microinjected into the DMV (n=7), but not into the NTS, blocked the vago-vagal 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.




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