title: alpha-bungarotoxin-sensitive nicotinic receptors indirectly modulate [(3)H]dopamine release in rat striatal slices via glutamate release.
abstract: Nicotinic agonists elicit the release of dopamine from striatal synaptosomes by acting on presynaptic nicotinic acetylcholine receptors (nAChRs) on dopamine nerve terminals. Both alpha3beta2* and alpha4beta2 nAChR subtypes (but not alpha7* nAChRs) have been implicated. Here, we compared nAChR-evoked [(3)H]dopamine release from rat striatal synaptosome and slice preparations by using the nicotinic agonist anatoxin-a. In the more integral slice preparation, the concentration-response curve for anatoxin-a-evoked [(3)H]dopamine release was best fitted to a two-site model, giving EC(50) values of 241 nM and 5.1 microM, whereas only the higher-affinity component was observed in synaptosome preparations (EC(50) = 134 nM). Responses to a high concentration of anatoxin-a (25 microM) in slices (but not in synaptosomes) were partially blocked by ionotropic glutamate receptor antagonists (kynurenic acid, 6,7-dinitroquinoxaline-2,3-dione) and by alpha7*-selective nAChR antagonists (alpha-bungarotoxin, alpha-conotoxin-ImI, methyllycaconitine) in a nonadditive manner. In contrast, the alpha3beta2-selective nAChR antagonist alpha-conotoxin-MII partially inhibited [(3)H]dopamine release from both slice and synaptosome preparations, stimulated with both low (1 microM) and high (25 microM) concentrations of anatoxin-a. Antagonism by alpha-conotoxin-MII was additive with that of alpha7*-selective antagonists. These data support a model in which alpha7* nAChRs on striatal glutamate terminals elicit glutamate release, which in turn acts at ionotropic glutamate receptors on dopamine terminals to stimulate dopamine release. In addition, non-alpha7* nAChRs on dopamine terminals also stimulate dopamine release. These observations have implications for the complex cholinergic modulation of inputs onto the major efferent neurons of the striatum.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Kaiser
authors.forename: S
authors.initials: S
authors.lastname: Wonnacott
mesh_terms: D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000145:classification; D011954:Receptors, Dopamine / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000145:classification; D014316:Tritium
chemical_list: D002038:Bungarotoxins; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D017470:Receptors, Glutamate; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D014316:Tritium; D018698:Glutamic Acid; D004298:Dopamine