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Vol. 294, Issue 1, 230-238, July 2000

Brainstem Nicotinic Receptor Subtypes That Influence Intragastric and Arterial Blood Pressures1

Manuel Ferreira, Anu Singh, Kenneth L. Dretchen, Kenneth J. Kellar and Richard A. Gillis

Department of Pharmacology, Georgetown University Medical Center, Washington, DC

The purpose of this study was to investigate the effect of microinjection of nicotine and nicotinic receptor antagonists into the dorsal motor nucleus of the vagus (DMV) or medial subnucleus of the tractus solitarius (mNTS) on intragastric (IGP) and arterial blood pressures (BP) in anesthetized rats. Nicotine microinjected into the DMV (10-300 pmol) produced dose-related increases in IGP (ED50 = 89 pmol); no significant changes were noted for BP. Ipsilateral vagotomy abolished nicotine-induced increases in IGP. Nicotine microinjected into the mNTS in a dose range of 0.1 to 300 pmol produced dose-related decreases in IGP (ED50 = 0.6 pmol) and BP (ED50 = 5.4 pmol). Bilateral vagotomy abolished nicotine-induced decreases in IGP while having no effect on BP. In rats treated with daily s.c. injections of nicotine (0.8 mg/kg of base) for 10 days, microinjections of nicotine into the DMV produced similar increases in IGP. BP responses from the mNTS were not affected by chronic treatment. However, nicotine microinjections into the mNTS no longer produced a decrease in IGP in these chronically treated animals. alpha -Bungarotoxin (100 pmol) significantly blocked nicotine-evoked increases in IGP from the DMV while having no effect on nicotine-induced responses elicited from the mNTS. Hexamethonium (10 and 100 pmol) microinjected into the mNTS dose-dependently blocked nicotine-induced effects but did not interfere with the action of nicotine at the DMV. Our data indicate that nicotine-induced changes in IGP result from nicotine acting at two sites, the DMV and mNTS; and that at least three different nicotinic receptors in the dorsal medulla oblongata can influence gastrointestinal and cardiovascular function.

1 This work was supported by a grant supplement (to M.F.) from the National Institute of Diabetes and Digestive and Kidney Diseases to Research Grant DK29975 (to R.A.G.). This work was completed as part of a Ph.D. thesis for Manuel Ferreira. This work was presented at the 1999 FASEB Meeting (abstract 374.2).

0022-3565/00/2941-0230$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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