Excitatory actions of dehydroabietic acid on mammalian synaptosomes.

Abstract

The presynaptic effects of dehydroabietic acid were investigated using mouse brain synaptosomes as the in vitro model. At concentrations ranging from 10 to 100 microM, dehydroabietic acid depolarises the synaptosomal membrane and causes pronounced release of the neurotransmitters gamma-aminobutyric acid, acetylcholine and L-glutamate. The effects on membrane potential and transmitter release occur predominantly at concentrations below which any lytic actions of this compound can be detected. Dehydroabietic acid-induced depolarisation and release of neurotransmitters are not influenced by tetrodotoxin and are associated with only marginal inhibition of membrane-associated ATPase activity. When synaptosomes are challenged with dehydroabietic acid in calcium-free saline, a partial reduction in the stimulated release of transmitters is observed. These results provide clear evidence that dehydroabietic acid is neuroactive and capable of causing substantial increases in the release of both excitatory and inhibitory neurotransmitter substances. The mechanism which underlies the neuroexcitatory effects of dehydroabietic acid remains to be resolved however it is proposed that release of transmitters from central nerve endings may be a contributory factor in the toxicity of resin acids.