Baclofen-induced, calcium-dependent stimulation of in vivo release of D-[3H]aspartate from rat hippocampus monitored by intracerebral microdialysis.
The release of D-[3H]aspartate (used as a tracer for endogenous glutamate and aspartate) was studied at high K+ (100 mM) and under ischemia in rats implanted with 0.3 mm diameter dialysis tubing through the hippocampus. The effect on the D-[3H]aspartate release of the two gamma-aminobutyric acid (GABA) agonists 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) and (+/-)-beta-(p-chlorophenyl)GABA (baclofen), which specifically activate GABAA and GABAB receptors, respectively, was studied. Initial experiments employing HPLC analysis showed a coincident increase in the amounts of glutamate, aspartate and the amount of radioactivity following introduction of K+ (100 mM) or a period of ischemia suggesting that the D-[3H]aspartate labels the transmitter pools of the two amino acids under the present experimental conditions. The presence of 10 mM baclofen or 10 mM THIP in the perfusion medium did not inhibit ischemia induced D-[3H]aspartate release. On the contrary, 10 mM baclofen alone (but not 0.1 or 1 mM) in the perfusion medium induced release of D-[3H]aspartate in a calcium dependent manner, whereas 10 mM THIP had no significant releasing effect.
Nielsen
E O
EO
Department of Chemistry BC, Royal Danish School of Pharmacy, Copenhagen.
Aarslew-Jensen
M
M
Diemer
N H
NH
Krogsgaard-Larsen
P
P
Schousboe
A
A
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001418:Baclofen / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D018756:GABA Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D018756:GABA Antagonists; D007555:Isoxazoles; D001224:Aspartic Acid; D001418:Baclofen; C015542:gaboxadol; D011188:Potassium; D002118:Calcium