Vol. 296, Issue 2, 260-269, February 2001

Evidence of a Functional 7-Neuronal Nicotinic Receptor Subtype Located on Motoneurons of the Dorsal Motor Nucleus of the Vagus

Manuel Ferreira, Steven N. Ebert, David C. Perry, Robert P. Yasuda, Chandra M. Baker, Martha I. Dávila-García, Kenneth J. Kellar and Richard A. Gillis

Departments of Pharmacology, Georgetown University School of Medicine (M.F., S.N.E., R.P.Y., C.M.B., M.I.D.-G., K.J.K., R.A.G.), Washington, DC, and George Washington University School of Medicine (D.C.P.), Washington, DC

In vitro autoradiography using ¹²⁵I--bungarotoxin (-BGTx) and anti-7 immunohistochemistry were performed on the dorsal motor nucleus of the vagus (DMV) of sham and chronically vagotomized rats to determine whether the 7-nicotinic acetylcholine receptor (nAChR) is located postsynaptically on DMV neurons whose axons contribute to the vagus nerve. Intense bilateral ¹²⁵I--BGTx binding and anti-7 immunostaining were observed in coronal brain sections containing the DMV of sham-vagotomized animals. Unilateral cervical vagotomy resulted in ipsilateral losses of ¹²⁵I--BGTx binding and anti-7 immunostaining from the DMV. Simultaneous staining of rat brainstem sections with anti-7 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 7-staining as well. In vagotomized animals, no ChAT-positive neurons expressing 7-nAChRs remained in the ipsilateral DMV. We conclude that the 7-nAChR subtype is located postsynaptically on DMV neurons. To test whether the 7-nAChR is similar to the 7-homomeric nAChR, experiments were performed in anesthetized rats, and compounds were microinjected into the DMV while monitoring intragastric pressure (IGP). -BGTx and strychnine antagonized nicotine-induced increases in IGP; no antagonism was observed with methyllycaconitine, a compound known to block the homomeric 7-nAChR subtype. Recovery from -BGTx-induced antagonism of the nicotine response was observed. We conclude that there is a nAChR containing the 7-subunit in the DMV that is different from the homomeric 7-nAChR subtype.