Inhibitory effects of arachidonic acid on nicotinic transmission in bullfrog sympathetic neurons

Arachidonic acid (AA, 0.2-40 mu M) reversibly reduced the amplitude of the fast excitatory postsynaptic potentials and the underlying currents (fast EPSCs) of bullfrog sympathetic neurons evoked by preganglionic nerve stimulation in a Ca2+-deficient solution. AA reduced the acetylcholine (ACh)-induced nicotinic currents (nIAch) evoked by brief applications of ACh to the ganglion cells in a dose-related manner. AA reduced the maximum amplitude of nI(ACh) estimated from the dose-response relationship without causing an appreciable change in the apparent dissociation constant. Indomethacin (2 mu M) and nordihydroguaiaretic acid (20 mu M), blockers of cyclooxygenase and lipoxygenase pathways, respectively, had no effect on the inhibition of fast EPSC by AA. AA did not obviously affect the preganglionic nerve terminal spike configuration, synaptic delay, facilitation, quantal content of transmitter release, or the presynaptic long-term potentiation elicited by the repetitive stimulation applied to the preganglionic nerve fibers. These results suggest that AA acts on an allosteric site of the nicotinic receptor-channel complex either directly or indirectly and in turn inhibits ion permeation through these channels without affecting the release of ACh from preganglionic nerve terminals.