melitten and baicalein

Depolarization-evoked increases in intraterminal free Ca2+ are required for the induction of neurotransmitter release from nerve terminals. Although the mechanisms that regulate the voltage-induced accumulation of presynaptic Ca2+ remain obscure, there is evidence that the phospholipase-dependent accumulation of arachidonic acid, or its metabolites, may be involved. Therefore, fura-2 loaded hippocampal mossy fiber nerve endings were used to investigate the relationships between membrane depolarization, lipid metabolism and presynaptic Ca2+ availability. It was observed that depolarization of the nerve terminals with KCl induced an increase in intraterminal free calcium that was inhibited more than 90% by a combination of voltage-sensitive Ca2+ channel blockers. In addition, the K(+)-dependent effects on Ca2+ concentrations were attenuated in the presence of phospholipase A2 inhibitors, but were mimicked by the phospholipase A2 activator melittin and exogenous arachidonic acid. Both the melittin- and arachidonic acid-induced increases in presynaptic Ca2+ were reduced by voltage-sensitive Ca2+ channel blockers. The stimulatory effects of arachidonic acid appeared to be independent of its further metabolism to prostaglandins. In fact, inhibition of either cyclooxygenase or lipoxygenase pathways resulted in a potentiation of the depolarization-evoked increase in intraterminal free Ca2+. From these results, we propose that some portion of the depolarization-evoked increase in intraterminal free calcium depends on the activation of phospholipase A2 and the subsequent accumulation of unesterified arachidonic acid.

Topics: Action Potentials; Animals; Arachidonic Acid; Calcium; Fatty Acids; Flavanones; Flavonoids; Hippocampus; Ibuprofen; Lipase; Melitten; Nerve Endings; Phospholipases A; Phospholipases A2; Potassium Chloride; Prostaglandins; Rats; Rats, Sprague-Dawley; Synaptosomes; Tetrodotoxin