PT - JOURNAL ARTICLE AU - Simone Sbrenna AU - Matteo Marti AU - Michele Morari AU - Girolamo Calo AU - Remo Guerrini AU - Lorenzo Beani AU - Clementina Bianchi TI - <span class="sc">l</span>-Glutamate and γ-Aminobutyric Acid Efflux from Rat Cerebrocortical Synaptosomes: Modulation by κ- and μ- but Not δ- and Opioid Receptor Like-1 Receptors DP - 1999 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1365--1371 VI - 291 IP - 3 4099 - http://jpet.aspetjournals.org/content/291/3/1365.short 4100 - http://jpet.aspetjournals.org/content/291/3/1365.full SO - J Pharmacol Exp Ther1999 Dec 01; 291 AB - The modulation by δ-, κ-, μ-, and opioid receptor like-1 (ORL1) agonists and antagonists ofl-glutamate (l-Glu) and γ-aminobutyric acid (GABA) efflux from superfused rat cerebrocortical synaptosomes was studied. Tetrodotoxin (0.5 μM) inhibited the spontaneous efflux of both transmitters by 20%. Ca2+ omission decreased GABA and facilitated l-Glu efflux. The neurotransmitter overflow evoked by K+ concentrations in the 7.5- to 10-mM range was largely Ca2+ dependent and tetrodotoxin sensitive. Neither the δ-receptor agonist deltorphin (up to 0.3 μM) nor the ORL1 receptor agonist nociceptin (up to 1 μM) significantly affected either spontaneous or K+-evoked neurotransmitter efflux. Conversely, the ORL1 ligand [Phe1(CH2-NH)Gly2]nociceptin(1–13)NH2(0.3 μM) caused a naloxone-sensitive inhibition of bothl-Glu- and GABA-stimulated overflow. The κ-receptor agonist (−)-U50,488 failed to modulate spontaneous l-Glu and GABA efflux. However, it similarly inhibited the K+-evoked overflow of both neurotransmitters (EC50 ∼100 nM; Emax∼25–30% inhibition) in a norbinaltorphimine-sensitive manner. The selective μ-receptor agonist endomorphin 1 inhibited both spontaneous (EC50 ∼50 nM) and K+-evoked (EC50∼10 nM; Emax ∼50% inhibition)l-Glu efflux in a naloxone-sensitive manner. Conversely, it significantly inhibited only K+-evoked GABA efflux (EC50 ∼10 nM), although with a lower maximal effect (Emax ∼25–30% inhibition). It is concluded that, in the rat cerebral cortex, l-Glu and GABA efflux from nerve terminals is under the direct inhibitory control of κ- and μ- (but not δ- or ORL1) receptors. Because glutamatergic terminals emerged as a preferential target of μ-receptor agonists, the activation of this receptor may advocate both relevant analgesic and neuroprotective effects. The American Society for Pharmacology and Experimental Therapeutics