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J Physiol Volume 545, Number 3, 1007-1016, December 15, 2002 DOI: 10.1113/jphysiol.2002.021337
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Journal of Physiology (2002), 545.3, pp. 1007-1016
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.021337

Nicotinic ACh receptor subtypes on gastrointestinally projecting neurones in the dorsal motor vagal nucleus of the rat

Niaz Sahibzada *†, Manuel Ferreira Jr *, Bernice Williams †, Adam Wasserman *, Stefano Vicini ‡ and Richard A. Gillis *

Departments of * Pharmacology and ‡ Physiology & Biophysics, Georgetown University Medical Center and † Department of Psychology, University of DC, Washington, DC, USA

To determine the predominant nicotinic ACh receptor (nAChR) located on neurones in the dorsal motor nucleus of the vagus (DMV) that project to the gastrointestinal tract, we used the rat brainstem slice preparation and whole-cell recordings of DMV neurones identified by retrograde DiI tracing to pharmacologically characterize nAChRs. Pressure ejection of acetylcholine (ACh, 250 µM for 200 ms) from a patch pipette placed ~10-20 µm from the surface of the recorded cell produced an inward current in most DMV neurones sampled. The average currents for neurones projecting to the fundus, antrum and caecum were 149 ± 38 (n = 25), 115 ± 18 (n = 29) and 117 ± 23 pA (n = 6), respectively. Blockade of the alpha7 subtype of nAChR with either alpha-bungarotoxin (alpha-BGT) or methyllycaconitine (MLA) counteracted 60-75 % of the ACh-evoked current in DMV neurones projecting to the fundus, antrum and caecum. In neurones projecting to the fundus and the antrum, currents resistant to alpha-BGT were significantly blocked by dihydro-beta-erythroidine (10-20 nM), an antagonist of the alpha4beta2 subtype of nAChR. In neurones projecting to the caecum, currents resistant to alpha-BGT were significantly depressed by a low concentration of mecamylamine (1 µM). Cytisine (100 µM), an agonist of nAChRs that contain the alpha7 or the beta4 subunit, evoked significant currents in caecum-projecting neurones that were previously exposed to alpha-BGT. In contrast, cytisine had no effect on DMV neurones previously exposed to alpha-BGT that project to the fundus or antrum. Our data indicate that the prevailing nAChR subtype in DMV neurones projecting to the GI tract is the alpha7 subtype. In addition, we obtained evidence for the co-expression of the alpha4beta2 nAChR subtype on DMV neurones projecting to the fundus and antrum, and the alpha3beta4 nAChR subtype on DMV neurones projecting to the caecum.



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