title: Glycinergic nerve endings in hippocampus and spinal cord release glycine by different mechanisms in response to identical depolarizing stimuli.
abstract: Studies on hippocampal glycine release are extremely rare. We here investigated release from mouse hippocampus glycinergic terminals selectively pre-labelled with [(3)H]glycine through transporters of the GLYT2 type. Purified synaptosomes were incubated with [(3)H]glycine in the presence of the GLYT1 blocker NFPS to abolish uptake (approximately 30%) through GLYT1. The non-GLYT1-mediated uptake was entirely sensitive to the GLYT2 blocker Org25543. Depolarization during superfusion with high-K(+) (15-50 mmol/L) provoked overflows totally dependent on external Ca(2+), whereas in the spinal cord the 35 or 50 mmol/L KCl-evoked overflow (higher than that in hippocampus) was only partly dependent on extraterminal Ca(2+). In the hippocampus, the Ca(2+)-dependent 4-aminopyridine (1 mmol/L)-evoked overflow was five-fold lower than that in spinal cord. The component of the 10 mumol/L veratridine-induced overflow dependent on external Ca(2+) was higher in the hippocampus than that in spinal cord, although the total overflow in the hippocampus was only half of that in the spinal cord. Part of the veratridine-evoked hippocampal overflow occurred by GLYT2 reversal and part by bafilomycin A(1)-sensitive exocytosis dependent on cytosolic Ca(2+) generated through the mitochondrial Na(+)/Ca(2+) exchanger. As glycine sites on NMDA receptors are normally not saturated, understanding mechanisms of glycine release should facilitate pharmacological modulation of NMDA receptor function.
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Luccini
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.forename: Luca
authors.initials: L
authors.lastname: Raiteri
mesh_terms: D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012521:Sarcosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
chemical_list: C435025:N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-3-(4'-phenylphenoxy)propyl)sarcosine; D011189:Potassium Chloride; D014701:Veratridine; D005998:Glycine; D012521:Sarcosine