Melittin enhances excitatory amino acid release and AMPA-stimulated 45Ca2+ influx in cultured neurons.
Melittin, a potent activator of phospholipase A2, enhanced both spontaneous and depolarization-induced release of D-[3H]aspartate in primary cultures of cerebellar granule cells. The action of melittin was concentration-dependent (EC50 value = 300 ng/ml) and did not require the presence of extracellular Ca2+. Melittin also stimulated the release of glutamate and aspartate, in addition to other endogenous amino acids (taurine, alanine and gamma-aminobutyric acid). These effects were accompanied by an enhanced influx of 45Ca2+, which was in part mediated by the activation of excitatory amino acid receptors by endogenous agonists. Low concentrations of melittin (50 ng/ml) potentiated the efficacy of AMPA in stimulating 45Ca2+ influx without affecting stimulation by kainate or by glutamate added in the absence of extracellular Mg2+ (a condition that favors the activation of NMDA receptors). These results indicate that activation of phospholipase A2 evokes both an enhanced glutamate release and an increased sensitivity of AMPA receptors, two events that may support synaptic facilitation and LTP formation.
Aronica
E
E
Institute of Pharmacology, University of Catania, School of Medicine, Italy.
Casabona
G
G
Genazzani
A A
AA
Catania
M V
MV
Contestabile
A
A
Virgili
M
M
Nicoletti
F
F
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D006098:Granulocytes / Q000378:metabolism; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008555:Melitten / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D009994:Osmolar Concentration; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D002132:Calcium Radioisotopes; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D008555:Melitten; D007051:Ibotenic Acid; D001224:Aspartic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium