Nicotine‐Stimulated Release of [3H]Norepinephrine from Fetal Rat Locus Coeruleus Cells in Culture

• Published in: Journal of neurochemistry Vol. 70; no. 2; pp. 663 - 670
• Main Authors: Gallardo, Kathy A., Leslie, Frances M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-02-1998; Blackwell
• Subjects: Alkaloids - pharmacology; Animals; Azocines; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Calcium - pharmacology; Cells, Cultured; Development; Dimethylphenylpiperazinium Iodide - pharmacology; Fetus; Locus Coeruleus - cytology; Locus Coeruleus - metabolism; Medical sciences; N-Methylaspartate - pharmacology; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Nicotine - pharmacology; Nicotinic acetylcholine receptor; Nicotinic Agonists - pharmacology; Norepinephrine - metabolism; Potassium Chloride - pharmacology; Pyridines - pharmacology; Quinolizines; Rats; Rats, Sprague-Dawley; Rhombencephalon - cytology; Rhombencephalon - metabolism; Structure-Activity Relationship; Tetrodotoxin - pharmacology; Tobacco, tobacco smoking; Toxicology; Tritium; Rat; Rodentia; Central nervous system; Tobacco smoking; Catecholamine; Cholinergic receptor; Vertebrata; Mammalia; Development; Fetus; Norepinephrine; Nicotinic receptor; Locus coeruleus; Brain (vertebrata); Nicotine
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.70020663.x

: Acute nicotine administration stimulated [3H]norepinephrine ([3H]NE) release from cultured fetal locus coeruleus (LC) cells. The effect was concentration dependent, with an EC50 of 0.9 µM, and was abolished by removal of calcium from, or addition of tetrodotoxin (500 nM) to, the assay buffer. Other nicotinic receptor agonists stimulated [3H]NE release, with the rank order of potency being (±)‐epibatidine > (−)‐nicotine > 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP). Whereas (−)‐nicotine and (±)‐epibatidine exhibited equal maximal responses, DMPP was a partial agonist and (−)‐cytisine had no agonist activity. Nicotine‐stimulated release of [3H]NE was blocked by nicotinic receptor antagonists, with an order of potency of mecamylamine > lobeline > cytisine > methyllycaconitine > dihydro‐β‐erythroidine. The pharmacological profile of this nicotinic receptor is largely consistent with that described previously for an α4β2 subunit combination, although discrepancies in the efficacies of agonists were observed. No additivity in NMDA‐ and nicotine‐stimulated [3H]NE release was observed, suggesting a common signal transduction mechanism. However, the pharmacological characteristics of MK‐801 blockade of nicotine‐induced responses were not consistent with those of an NMDA receptor. We therefore conclude that nicotine directly releases [3H]NE from LC cells and does not act indirectly via activation of glutamate release.