alpha-bungarotoxin-sensitive nicotinic receptors indirectly modulate [(3)H]dopamine release in rat striatal slices via glutamate release.

Content Provider	Semantic Scholar
Author	Kaiser, S. A. Wonnacott, Susan
Copyright Year	2000
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.
File Format	PDF HTM / HTML
DOI	10.1124/mol.58.2.312
PubMed reference number	10908298
Journal	Medline
Volume Number	58
Issue Number	2
Alternate Webpage(s)	http://molpharm.aspetjournals.org/content/molpharm/58/2/312.full.pdf
Alternate Webpage(s)	https://doi.org/10.1124/mol.58.2.312
Journal	Molecular pharmacology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article