Different presynaptic nicotinic receptor subtypes modulate in vivo and in vitro the release of glycine in the rat hippocampus

作者：Zappettini Stefania; Mura Elisa; Grilli Massimo; Preda Stefania; Salamone Alessia; Olivero Guendalina; Govoni Stefano; Marchi Mario^*

来源：Neurochemistry International, 2011, 59(5): 729-738.

DOI：10.1016/j.neuint.2011.06.022

• Synaptosomes
• Glycine
• Nicotinic receptor subtypes
• Hippocampus
• In vivo release
• In vitro release

In the present study. using an in vivo approach (a microdialysis technique associated to HPLC with fluorimetric detection) and in vitro purified hippocampal synaptosomes in superfusion, we investigated the glycinergic transmission in the hippocampus, focusing on the nicotinic control of glycine (GLY) release. The acute administration of nicotine in vivo was able to evoke endogenous GLY release in the rat hippocampus. The specific nicotinic agonists PHA-543613 hydrochloride (PHA543613) selective for the alpha 7 nicotinic receptor subtype administered in vivo also elicited GLY release in a similar extent, while the alpha 4 beta 2 agonist 5-IA85380 dihydrochloride (5IA85380) was less effective. Nicotine elicited GLY overflow also from hippocampal synaptosomes in vitro. This overflow was Ca(2+)-dependent and inhibited by methyllycaconitine (MLA), but was not modified by dihydro-beta-erythroidine (DH beta E, 1 mu M). Choline(Ch)-evoked GLY overflow was Ca(2+) dependent, unaltered in presence of DH beta E and blocked by methyllycaconitine (MLA). Additionally, 5IA85380 elicited a GLY overflow, which in turn was Ca2+ dependent, was significantly inhibited by DH beta E but was unaffected by MLA. The GLY overflow produced by these nicotinic agonists quantitatively resembles that evoked by 9 mM KCl. The effects of a high concentration of 5IA85380 (1 mM), in the presence of 2 mu M DH beta E, on the release of GLY was also studied comparatively to that on glutamate and aspartate release. The nicotinic agonist 5IA85380 tested at high concentration (1 mM) was able to produce a stimulatory effect of endogenous release of the three amino acids, even in the presence of 2 mu M DH beta E, indicating the existence of a DH beta E resistant, alpha 4 beta 2 nAChR subtype with a functional role in the modulation of GLY. ASP, and GLU release. Our results show that in the rat hippocampus the release of GLY is, at least in part, of neuronal origin and is modulated by the activation of both alpha 7 and alpha 4 beta 2 (low and high affinity) nAChR subtypes.

• 出版日期2011-10