The influence of an inhibitor of lipoxygenases on the modulation of the plasticity of cholinoreceptors by 15-HETE.

The role of acyclic eicosanoids in the modulation of the plasticity of somatic cholinoreceptors by 15(S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (15-HETE) was investigated in identified RPa3 and LPa3 neurons of Helix lucorum using the two-electrode voltage clamping technique. It was demonstrated that the inhibitor of lipoxygenases, nordihydroguaiaretic acid (2-20 microM), completely blocks the short- and long-latency effects of 15-HETE (2-20 microM) on the depth of damping of the inward current induced by rhythmic applications of acetylcholine (ACh) to the soma. It is concluded that the short-latency effect of 15-HETE on the plasticity of cholinoreceptors is determined by its inhibition mainly of 5-lipoxygenase, which leads to a reduction in the level of acyclic eicosanoids that are formed under the influence of this enzyme. The potentiation of the effects of the acyclic eicosanoids, whose synthesis is resumed in the second phase, probably underlies the direct long-latency modulatory effect of 15-HETE.