Direct evidence that release‐stimulating α7* nicotinic cholinergic receptors are localized on human and rat brain glutamatergic axon terminals

Journal of Neurochemistry - Tập 80 Số 6 - Trang 1071-1078 - 2002
Mario Marchi1, Francesca Risso1, Concetta Viola2, Paolo Cavazzani3, Maurizio Raiteri1
1Sezione di Farmacologia e Tossicologia, Dipartimento di Medicina Sperimentale, Università di Genova, Genoa, Italy
2Clinica Neurochirurgica, Ospedale S. Martino, Università di Genova, Genoa, Italy
3Divisione di Neurochirurgia, Ospedali Galliera, Genoa, Italy

Tóm tắt

Abstract

The existence on glutamatergic nerve endings of nicotinic acetylcholine receptors (nAChRs) mediating enhancement of glutamate release has often been suggested but not demonstrated directly. Here, we study the effects of nAChR agonists on [3H]‐d‐aspartate ([3H]‐d‐ASP) release from synaptosomes superfused in conditions known to prevent indirect effects. Nicotinic receptor agonists, while unable to modify the basal [3H]‐d‐ASP release from human neocortex or rat striatal synaptosomes, enhanced the Ca2+‐dependent exocytotic release evoked by K+ (12 mm) depolarization. Their rank order of potency were anatoxin‐a > epibatidine > nicotine > ACh (+ atropine). The anatoxin‐a effect, both in human and rat synaptosomes, was antagonized by mecamylamine, α‐bungarotoxin or methyllycaconitine. The basal release of [3H]ACh from human cortical synaptosomes was increased by (–)‐nicotine (EC50 = 1.16 ± 0.33 µm) or by ACh plus atropine (EC50 = 2.0 ± 0.04 µm). The effect of ACh plus atropine was␣insensitive to α‐bungarotoxin, methyllycaconitine or α‐conotoxin MII, whereas it was totally antagonized by mecamylamine or dihydro‐β‐erythroidine. To conclude, glutamatergic axon terminals in human neocortex and in rat striatum possess α7* nicotinic heteroreceptors mediating enhancement of glutamate release. Release‐enhancing cholinergic autoreceptors in human neocortex are nAChRs with a pharmacological profile compatible with the α4β2 subunit combination.

Từ khóa


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Journal of Neurochemistry

Tập 80 Số 6

1071-1078

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