Linoleoylamide is physiological constituent of neurons. The effects of this agent, also a sleep-inducing agent, on ion currents in pituitary GH3 cells were investigated. Hyperpolarization-elicited K+ currents in GH3 cells bathed in a high-K+, Ca2+-free solution were studied to determine the effects of linoleoylamide and other related compounds on the IK(IR) that was sensitive to inhibition by E-4031 and identified as an erg (ether-à-go-go-related-gene) current. Linoleoylamide suppressed the amplitude of IK(IR) in a concentration-dependent manner with an IC50 value of 5 μM. Oleamide (20 μM) inhibited the amplitude of IK(IR), while neither arachidonic acid (20 μM) nor 14,15-epoxyeicosatrienoic acid (20 μM) had an effect on it. In GH3 cells incubated with anandamide (20 μM) or arachidonic acid (20 μM), the linoleoylamide-induced inhibition of IK(IR) remained unaltered. In inside-out patches, arachidonic acid (20 μM) and 14,15-epoxyeicosatrienoic acid (20 μM) stimulated large-conductance Ca2+-activated K+ channels; however, linoleoylamide (20 μM) had little or no effect on them. Under current-clamp mode, linoleoylamide (20 μM) increased the firing rate. In IMR-32 neuroblastoma cells, linoleoylamide also suppressed IK(IR). This study provides the evidence that linoleoylamide has a depressant effect on the erg current, and suggests that this effect may affect hormonal secretion.
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