Characterization of nicotinic receptors involved in the release of noradrenaline from the hippocampus

• Published in: Neuroscience Vol. 77; no. 1; pp. 121 - 130
• Main Authors: Sershen, H, Balla, A, Lajtha, A, Vizi, E.S
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-01-1997; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Calcium Channels - chemistry; Calcium Channels - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dentate Gyrus - chemistry; Dentate Gyrus - drug effects; Dentate Gyrus - metabolism; Dimethylphenylpiperazinium Iodide - pharmacology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; hippocampus; nicotinic acetylcholine receptor; Nicotinic Agonists - pharmacology; Nicotinic Antagonists - pharmacology; noradrenaline release; noradrenergic receptor; Norepinephrine - metabolism; Norepinephrine - pharmacokinetics; Organ Culture Techniques; presynaptic receptors; Presynaptic Terminals - chemistry; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - chemistry; Receptors, Nicotinic - metabolism; subtypes; Tetrodotoxin - pharmacology; Tritium; Vertebrates: nervous system and sense organs; DMPP, dimethylphenylpiperazinium; hippocampus; FRR, fractional resting release; noradrenaline release; nAChR, nicotinic acetylcholine receptor; NA, noradrenaline; DHβE, dihydro-β-erythroidine; DG, dentate gyrus; noradrenergic receptor; subtypes; ACh, acetylcholine; EGTA, ethyleneglycolbis(aminoethyl ether)tetra-acetate; presynaptic receptors; nicotinic acetylcholine receptor; Cholinergic receptor; Vertebrata; Mammalia; Rat; Rodentia; Central nervous system; Norepinephrine; Catecholamine; Nicotinic receptor; Hippocampus; Release; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(96)00425-3

The pharmacological features of putative nicotinic acetylcholine receptor sites involved in the release of [
3H]noradrenaline were assessed in rat hippocampus. The effect of nicotinic agonists to induce [
3H]noradrenaline release was examined in superfused slices. The nicotinic agonists (−)-epibatidine, (+)-anatoxin-a, dimethylphenylpiperazinium, (−)-nicotine and (−)-lobeline released [
3H]noradrenaline. The dose–response curves to nicotinic agonists were bell shaped, and indicated that their functional efficacies and potency vary across agonists. Maximal efficacy was seen with dimethylphenylpiperazinium and lobeline (
E
max values two to three times higher than other agonists). The rank order of potency for the agonists to release [
3H]noradrenaline was (−)-epibatidine
>
(+)-anatoxin-a
>
dimethylphenylpiperazinium
>
cytisine
>
nicotine
>
(−)-lobeline. The nicotinic acetylcholine receptor antagonists [n-bungarotoxin
>
mecamylamine>(+)-tubocurarine
>
hexamethonium≫α-bungarotoxin=dihydro-β-erythroidine] and tetrodotoxin antagonized the effect of dimethylphenylpiperazinium to release [
3H]noradrenaline. The results, based on these pharmacological profiles, suggest the possible involvement of nicotinic acetylcholine receptor α3 and β2 nicotinic acetylcholine receptor subunits in the control of [
3H]noradrenaline release from hippocampal slices. The absence of effect of α-bungarotoxin and α-conotoxin-IMI excludes the possible involvement of nicotinic acetylcholine receptors containing the α7 subunit. The release of [
3H]noradrenaline by dimethylphenylpiperazinium was Ca
2+ dependent. Nifedipine failed to prevent the dimethylphenylpiperazinium-induced release of [
3H]noradrenaline, but Cd
2+, ω-conotoxin and Ca
2+-free conditions significantly reduced the dimethylphenylpiperazinium-induced release, suggesting that N-type voltage-sensitive Ca
2+ channels are involved in the nicotinic acetylcholine receptor response. These voltage-sensitive Ca
2+ channels are activated by the local depolarization produced by sodium influx through the nicotinic channels activated by dimethylphenylpiperazinium.
Thus, the observed tetrodotoxin sensitivity of dimethylphenylpiperazinium-induced release of [
3H]noradrenaline can be explained either by local depolarization and subsequent generation of action potentials at the preterminal area or that these nicotinic acetylcholine receptors are located on interneurons rather than directly on noradrenergic terminals.