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Research ArticleCARDIOVASCULAR

Brainstem Nicotinic Receptor Subtypes That Influence Intragastric and Arterial Blood Pressures

Manuel Ferreira, Anu Singh, Kenneth L. Dretchen, Kenneth J. Kellar and Richard A. Gillis
Journal of Pharmacology and Experimental Therapeutics July 2000, 294 (1) 230-238;
Manuel Ferreira
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Anu Singh
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Kenneth L. Dretchen
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Kenneth J. Kellar
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Richard A. Gillis
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Abstract

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. α-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.

Footnotes

  • Send reprint requests to: Richard A. Gillis, Ph.D., Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Rd., NW, Washington, DC 20007. E-mail:GILLISR{at}gunet.georgetown.edu

  • ↵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).

  • Abbreviations:
    GI
    gastrointestinal
    DMV
    dorsal motor nucleus of the vagus
    mNTS
    medial subnucleus of the tractus solitarius
    nAChR
    nicotinic acetylcholine receptor
    NA
    nucleus ambiguus
    CS
    calamus scriptorius
    IGP
    intragastric pressure
    AP
    area postrema
    TS
    solitary tract
    CC
    central canal
    BP
    arterial blood pressure
    • Received November 29, 1999.
    • Accepted March 8, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 1
1 Jul 2000
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Research ArticleCARDIOVASCULAR

Brainstem Nicotinic Receptor Subtypes That Influence Intragastric and Arterial Blood Pressures

Manuel Ferreira, Anu Singh, Kenneth L. Dretchen, Kenneth J. Kellar and Richard A. Gillis
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 230-238;

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Research ArticleCARDIOVASCULAR

Brainstem Nicotinic Receptor Subtypes That Influence Intragastric and Arterial Blood Pressures

Manuel Ferreira, Anu Singh, Kenneth L. Dretchen, Kenneth J. Kellar and Richard A. Gillis
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 230-238;
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