Evidence of a functional alpha7-neuronal nicotinic receptor subtype located on motoneurons of the dorsal motor nucleus of the vagus

J Pharmacol Exp Ther. 2001 Feb;296(2):260-9.

Abstract

In vitro autoradiography using 125I-alpha-bungarotoxin (alpha-BGTx) and anti-alpha7 immunohistochemistry were performed on the dorsal motor nucleus of the vagus (DMV) of sham and chronically vagotomized rats to determine whether the alpha7-nicotinic acetylcholine receptor (nAChR) is located postsynaptically on DMV neurons whose axons contribute to the vagus nerve. Intense bilateral 125I-alpha-BGTx binding and anti-alpha7 immunostaining were observed in coronal brain sections containing the DMV of sham-vagotomized animals. Unilateral cervical vagotomy resulted in ipsilateral losses of 125I-alpha-BGTx binding and anti-alpha7 immunostaining from the DMV. Simultaneous staining of rat brainstem sections with anti-alpha7 and anti-choline acetyltransferase (ChAT) antibodies (to identify cholinergic DMV neurons that project into the vagus nerve) revealed that every DMV neuron that was stained for ChAT showed alpha7-staining as well. In vagotomized animals, no ChAT-positive neurons expressing alpha7-nAChRs remained in the ipsilateral DMV. We conclude that the alpha7-nAChR subtype is located postsynaptically on DMV neurons. To test whether the alpha7-nAChR is similar to the alpha7-homomeric nAChR, experiments were performed in anesthetized rats, and compounds were microinjected into the DMV while monitoring intragastric pressure (IGP). alpha-BGTx and strychnine antagonized nicotine-induced increases in IGP; no antagonism was observed with methyllycaconitine, a compound known to block the homomeric alpha7-nAChR subtype. Recovery from alpha-BGTx-induced antagonism of the nicotine response was observed. We conclude that there is a nAChR containing the alpha7-subunit in the DMV that is different from the homomeric alpha7-nAChR subtype.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aconitine / analogs & derivatives*
  • Aconitine / pharmacology
  • Animals
  • Autoradiography
  • Bungarotoxins / pharmacokinetics
  • Bungarotoxins / pharmacology
  • Fluorescein-5-isothiocyanate
  • Fluorescent Antibody Technique, Indirect
  • Male
  • Microinjections
  • Motor Neurons / metabolism*
  • Nicotinic Agonists / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism*
  • Stomach / drug effects
  • Vagotomy
  • Vagus Nerve / cytology
  • Vagus Nerve / metabolism*
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Bungarotoxins
  • Chrna7 protein, rat
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • methyllycaconitine
  • Fluorescein-5-isothiocyanate
  • Aconitine