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PMID: 8646402 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Release of [3H]-noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal [3H]-dopamine release.

British journal of pharmacology ·Vol. 117 ·No. 4 ·1996-02-00 ·Pages 595-606

Clarke PB, Reuben M

Abstract

1. The aim of the present experiment was to characterize nicotine-evoked [3H]-noradrenaline ([3H]-NA) release from rat superfused hippocampal synaptosomes, using striatal [3H]-dopamine release for comparison. 2. (-)-Nicotine, cytisine, DMPP and acetylcholine (ACh) (with esterase inhibitor and muscarinic receptor blocker) increased NA release in a concentration-dependent manner (EC50 6.5 microM, 8.2 microM, 9.3 microM, and 27 microM, respectively) with similar efficacy. 3. Nicotine released striatal dopamine more potently than hippocampal NA (EC50 0.16 microM vs. 6.5 microM). (+)-Anatoxin-a also increased dopamine more potently than NA (EC50 0.05 microM vs. 0.39 microM), and maximal effects were similar to those of nicotine. Isoarecolone (10-320 microM) released dopamine more effectively than NA but a maximal effect was not reached. (-)-Lobeline (10-320 microM) evoked dopamine release, but the effect was large and delayed with respect to nicotine; NA release was not increased but rather depressed at high concentrations of lobeline. High K+ (10 mM) released and NA to similar extents. 4. Addition of the 5-hydroxytryptamine (5-HT) reuptake blocker, citalopram (1 microM) to hippocampal synaptosomes affected neither basal NA release nor nicotine-evoked release. 5. The nicotinic antagonist, mecamylamine (10 microM), virtually abolished NA and dopamine release evoked by high concentrations of nicotine, ACh, cytisine, isoarecolone, and anatoxin-a. Although NA release evoked by DMPP (100 microM) was entirely mecamylamine-sensitive, DMPP-evoked dopamine release was only partially blocked. Dopamine release evoked by lobeline (320 microM) was completely mecamylamine-insensitive. 6. The nicotinic antagonists dihydro-beta-erythroidine and methyllycaconitine inhibited nicotine-evoked dopamine release approximately 30 fold more potently than NA release. In contrast, the antagonist chlorisondamine, displayed a reverse sensitivity, whereas trimetaphan and mecamylamine did not preferentially block either response. None of these antagonists, given at a high concentration, significantly altered release evoked by high K+. 7. Blockade of nicotine-evoked transmitter release by methyllycaconitine and dihydro-beta-erythroidine was surmounted by a high concentration of nicotine (100 microM), but blockade by mecamylamine, chlorisondamine, and trimetaphan was insurmountable. 8. Nicotine-evoked NA release was unaffected by tetrodotoxin, whereas veratridine-evoked NA release was virtually abolished. 9. We conclude that presynaptic nicotinic receptors associated with striatal dopamine and hippocampal NA terminals differ pharmacologically. In situ hybridization studies suggest that nigrostriatal dopaminergic neurones express mainly alpha 4, alpha 5, and beta 2 nicotinic cholinoceptor subunits, whereas hippocampal-projecting noradrenaline (NA) neurones express alpha 3, beta 2 and beta 4 subunits. Pharmacological comparisons of recombinant receptors suggest that release of hippocampal NA may be modulated by receptors containing alpha 3 and beta 4 subunits.

MeSH Terms
Acetylcholine/pharmacology Alkaloids/pharmacology Animals Azocines Bacterial Toxins/pharmacology Citalopram/pharmacology Corpus Striatum/metabolism Cyanobacteria Toxins Hippocampus/drug effects,metabolism In Vitro Techniques Male Marine Toxins/pharmacology Microcystins Nicotine/pharmacology Nicotinic Agonists/pharmacology Nicotinic Antagonists/pharmacology Norepinephrine/metabolism Potassium/metabolism Quinolizines Rats Rats, Sprague-Dawley Receptors, Nicotinic/classification,physiology Serotonin Antagonists/pharmacology Synaptosomes/drug effects,metabolism Tetrodotoxin/pharmacology Tritium Tropanes
Chemicals
Alkaloids Azocines Bacterial Toxins Cyanobacteria Toxins Marine Toxins Microcystins Nicotinic Agonists Nicotinic Antagonists Quinolizines Receptors, Nicotinic Serotonin Antagonists Tropanes Citalopram Tritium Tetrodotoxin cytisine Nicotine anatoxin a Acetylcholine Potassium Norepinephrine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Clarke P B
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Reuben M
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1996.tb15232.x
Published
1996-02-00
Pages
595-606
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1909326
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1476-5381.1996.tb15232.x PMC Full Text View journal details
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