The aim of this study was to verify the presence of presynaptic nicotinic acetylcholine receptors (nAChRs) at the terminals of myenteric motoneurons using a potent and highly selective nicotinic agonist, epibatidine. We examined contraction, and release of [3H]ACh on a guineapig longitudinal muscle strip preparation. First, we compared the ability of epibatidine and nicotine to induce isometric contraction and found epibatidine (EC50 = 23.1 nM) to be 300-fold more potent than nicotine (EC50 = 7.09 μM). The release and contraction induced by 30 nM epibatidine were inhibited by the nicotinic antagonist mecamylamine (3 μM) and the Na+-channel blocker TTX (1 μM), indicating that the effects are mediated via nAChRs and are fully dependent on the propagation of action potentials. Atropine (0.1 μM) significantly increased the [3H]ACh release but could not block contraction suggesting that a substantial part of the response develops via a noncholinergic mechanism. Epibatidine at a higher concentration (300 nM) induced contraction, which was only partly (45%) inhibited by TTX (1 μM). The TTX-resistant contraction, however, was completely blocked by mecamylamine (3 μM). Our data provide functional neurochemical evidence for the existence of presynaptic nAChRs at myenteric motoneuron terminals and suggest that these receptors can be activated only/by a higher concentration of agonists.
- Longitudinal muscle strip
- Myenteric plexus
- Presynaptic nicotinic acetylcholine receptors
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience