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A study on the release of 3H-glycine from preloaded hippocampal synaptosomes
144
Pharmacological Research, Vol. 26, Supplement 1, 1992
pros-METHYLIMIDAZOLEACETIC ACID-EVOKED RELEASE OF GLUTAMIC ACID FROM STRIATUM OF FREELY MOVING RATS Giovanna Cherici, Flavio Moroni, Jack Peter Green’ & Patririo Blandina Dip. di Farmacologia Preclinica e Clinica, Universita di Firenze (I) & *Dept. of Pharmacology, Mount Sinai School of Medicine, C.U.N.Y., New York (U.S.A.) In patients with Parkinson’s disease, cerebrospinal fluid levels of prosmethylimidazoleacetic acid (p-MIAA), an endogenous substance in brain and other tissues, were highly correlated with the severity of the disease (l), however, no causal relationship has been established. The possible contribution of the excitatory amino acids (EAA) to the neural toxicity in Parkinson’s disease prompted us to examine the effects of p-MIAA on release of glutamic (GLU) and aspartic (ASP) acids, using the technique of microdialysis. Male Wistar rats (2009) were implanted with dialysis fiber in the striatum, hippocampus or cortex. Twenty four hours later, baseline extracellular GLU and ASP were measured by HPLC coupled with fluorescent detection. Perfusion flow rate was 2 @/min. Striatum, hippocampus and cortex released spontaneously GLU and ASP in the micromolar range. After a minimum of five lo-min samples were collected, rats were given p-MIAA through the dialisys fiber. pMlAA (l-0.01 mM) produced a concentration-dependent increase of GLU but not of ASP striatal extracellular level. The maximal effect was two to three-fold the baseline. Interestingly, p-MIAA was ineffective on hippocampal and cortical levels of both EAAs, thus suggesting region-specificity. Since p-MIAA , up to 1 mM, did not alter the uptake of GLU by striatal slices, the presence of direct releasing mechanism(s) is suggested. (l)Prell GD, Khandelwal JK, Burns RS, Blandina P, Morrishow AM, Green JP. J.Neural Transm. 1991; 3:i 09-I 25.
A STUDY ON THE RELEASE OF 3H-GLYCINE FROM PRELOADED HIPPOCANPAL SYNAPTOSONES Monica Bargellini & Alessandro Galli Francesca Nori, Laura Coppini, Department of Preclinical and Clinical Pharmacology, University of Florence V.le G.B. Norgagni 65, 50134-Firenze. Italy and ouabaine upon the release of exogeThe effect of high K", veratridine nously-loaded 3H-glycine was evaluated in crude synaptosomal preparations from rat hipppocampi by means of a superfusion technique (II in the presence of media with different ionic compositions. 30 mN KCl, 10 UN veratridine and 0.4 mN ouabaine caused a significant increase in the radioactive efflux from synaptosomes. The omission of Caz+ in the superfusion medium markedly decreased K+-evoked 3H-glycine efflux, did not modify that evoked by veratridine and significantly increased that evoked by ouabaine. The substitution of Na+ with choline always resulted in a drastic decrease of the stimulated radioactive efflux from the synaptosomes. The omission of Cl- in the super-fusion medium generally resulted in a moderate increase of 3H-glycine release. These results suggest a functional release of glycine from hippocampal neurons following depolarizing stimuli. (11 Raiteri
N, Angelini
F. Levi
G.
Eur J Pharmacol
1974;
25:
411-14
Pharmacological Research, Vol. 26, Supplement 1, 1992
pros-METHYLIMIDAZOLEACETIC ACID-EVOKED RELEASE OF GLUTAMIC ACID FROM STRIATUM OF FREELY MOVING RATS Giovanna Cherici, Flavio Moroni, Jack Peter Green’ & Patririo Blandina Dip. di Farmacologia Preclinica e Clinica, Universita di Firenze (I) & *Dept. of Pharmacology, Mount Sinai School of Medicine, C.U.N.Y., New York (U.S.A.) In patients with Parkinson’s disease, cerebrospinal fluid levels of prosmethylimidazoleacetic acid (p-MIAA), an endogenous substance in brain and other tissues, were highly correlated with the severity of the disease (l), however, no causal relationship has been established. The possible contribution of the excitatory amino acids (EAA) to the neural toxicity in Parkinson’s disease prompted us to examine the effects of p-MIAA on release of glutamic (GLU) and aspartic (ASP) acids, using the technique of microdialysis. Male Wistar rats (2009) were implanted with dialysis fiber in the striatum, hippocampus or cortex. Twenty four hours later, baseline extracellular GLU and ASP were measured by HPLC coupled with fluorescent detection. Perfusion flow rate was 2 @/min. Striatum, hippocampus and cortex released spontaneously GLU and ASP in the micromolar range. After a minimum of five lo-min samples were collected, rats were given p-MIAA through the dialisys fiber. pMlAA (l-0.01 mM) produced a concentration-dependent increase of GLU but not of ASP striatal extracellular level. The maximal effect was two to three-fold the baseline. Interestingly, p-MIAA was ineffective on hippocampal and cortical levels of both EAAs, thus suggesting region-specificity. Since p-MIAA , up to 1 mM, did not alter the uptake of GLU by striatal slices, the presence of direct releasing mechanism(s) is suggested. (l)Prell GD, Khandelwal JK, Burns RS, Blandina P, Morrishow AM, Green JP. J.Neural Transm. 1991; 3:i 09-I 25.
A STUDY ON THE RELEASE OF 3H-GLYCINE FROM PRELOADED HIPPOCANPAL SYNAPTOSONES Monica Bargellini & Alessandro Galli Francesca Nori, Laura Coppini, Department of Preclinical and Clinical Pharmacology, University of Florence V.le G.B. Norgagni 65, 50134-Firenze. Italy and ouabaine upon the release of exogeThe effect of high K", veratridine nously-loaded 3H-glycine was evaluated in crude synaptosomal preparations from rat hipppocampi by means of a superfusion technique (II in the presence of media with different ionic compositions. 30 mN KCl, 10 UN veratridine and 0.4 mN ouabaine caused a significant increase in the radioactive efflux from synaptosomes. The omission of Caz+ in the superfusion medium markedly decreased K+-evoked 3H-glycine efflux, did not modify that evoked by veratridine and significantly increased that evoked by ouabaine. The substitution of Na+ with choline always resulted in a drastic decrease of the stimulated radioactive efflux from the synaptosomes. The omission of Cl- in the super-fusion medium generally resulted in a moderate increase of 3H-glycine release. These results suggest a functional release of glycine from hippocampal neurons following depolarizing stimuli. (11 Raiteri
N, Angelini
F. Levi
G.
Eur J Pharmacol
1974;
25:
411-14