Title : Pharmacological and null mutation approaches reveal nicotinic receptor diversity - Whiteaker_2000_Eur.J.Pharmacol_393_123 |
Author(s) : Whiteaker P , Marks MJ , Grady SR , Lu Y , Picciotto MR , Changeux JP , Collins AC |
Ref : European Journal of Pharmacology , 393 :123 , 2000 |
Abstract :
We have developed an array of assays for nicotinic acetylcholine receptor binding and function. [125I]alpha-Bungarotoxin-, (-)-[3H]nicotine-, and [3H]epibatidine-binding nicotinic acetylcholine receptors were assayed in mouse brain membranes and sections. Nicotinic acetylcholine receptor function was quantified using synaptosomal [3H]dopamine, [3H]gamma-aminobutyric acid ([3H]GABA), and 86Rb(+) efflux techniques. Additionally, the effects of beta2 subunit deletion on each of the measures were assessed. Detailed pharmacological comparison revealed minimally six nicotinic binding subtypes: [125I]alpha-bungarotoxin-binding nicotinic acetylcholine receptors; beta2-subunit-dependent and -independent high-affinity (-)-[3H]nicotine-binding sites; beta2-dependent and -independent cytisine-resistant [3H]epibatidine-binding sites; and a beta2-dependent low-affinity [3H]epibatidine binding site. Comparative pharmacology suggested that [3H]GABA and dihydro-beta-erythroidine (DHbetaE)-sensitive 86Rb(+) efflux are mediated by the same (probably alpha4beta2) nicotinic acetylcholine receptor subtype, while other nicotinic acetylcholine receptor subtypes evoke [3H]dopamine and DHbetaE-resistant 86Rb(+) efflux. In whole-brain preparations, each measure of nicotinic acetylcholine receptor function was beta2 dependent. The majority of beta2-independent [3H]epibatidine binding was located in small, scattered brain nuclei, suggesting that individual nuclei may prove suitable for identification of novel, native nicotinic acetylcholine receptors. |
PubMedSearch : Whiteaker_2000_Eur.J.Pharmacol_393_123 |
PubMedID: 10771005 |
Whiteaker P, Marks MJ, Grady SR, Lu Y, Picciotto MR, Changeux JP, Collins AC (2000)
Pharmacological and null mutation approaches reveal nicotinic receptor diversity
European Journal of Pharmacology
393 :123
Whiteaker P, Marks MJ, Grady SR, Lu Y, Picciotto MR, Changeux JP, Collins AC (2000)
European Journal of Pharmacology
393 :123