Glycine stimulates [3H]noradrenaline release by activating a strychnine-sensitive receptor present in rat hippocampus.
Rat hippocampus slices were prelabeled with [3H]noradrenaline ([3H]NA) and depolarized by superfusion with KCl. The release evoked by 12 mM K+ was totally calcium-dependent and more than 90% tetrodotoxin (TTX)-sensitive. Glycine (0.1-1 mM) increased the K(+)-evoked [3H]NA overflow in a concentration-dependent manner. The effect of 1 mM glycine reached 300%. Strychnine (0.3 microM) shifted to the right the concentration-response curve for glycine. The effect of glycine (0.1 or 1 mM) was totally abolished by 3 microM strychnine but was unaffected by the GABAA receptor antagonist, bicuculline (10 microM), or by 100 microM of 1-hydroxy-3-aminopyrrolidone-2 (HA-966), a proposed antagonist of glycine at the strychnine-insensitive site located on the N-methyl-D-aspartate (NMDA) receptor. The effect of glycine was mimicked by L-serine, although less potently; the release of [3H]NA was enhanced by 200% in presence of 3 mM L-serine. At this concentration D-serine was ineffective. Strychnine shifted to the right the concentration-response curve for L-serine. Glycine (1 mM) had only a minor effect (less than 20% potentiation) on the release of [3H]NA evoked by 12 mM KCl in hippocampal synaptosomes. While the effect of glycine in slices was increased by decreasing the depolarizing concentration of K+ (about 500% potentiation at 9 mM K+), the response of synaptosomes remained minimal, even in presence of 9 mM KCl. Hippocampal synaptosomes prelabeled with [3H]glycine released the radiolabeled amino acid when exposed to superfusion with 12 mM KCl. The release of [3H]glycine was more than 75% calcium-dependent. The results suggest that the release of NA in rat hippocampus may be enhanced by glycine through the activation of a strychnine-sensitive receptor. This receptor does not seem to be located on noradrenergic terminals.
Raiteri
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M
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Fontana
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G
Fedele
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E
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D005998:Glycine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012694:Serine / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects; D014316:Tritium
D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D012694:Serine; C001369:1-hydroxy-3-amino-2-pyrrolidone; D013331:Strychnine; D011188:Potassium; D002118:Calcium; D005998:Glycine; D009638:Norepinephrine; D001640:Bicuculline