Block of erg current by linoleoylamide, a sleep-inducing agent, in pituitary GH3 cells

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 + ,C a 2+ -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-a`-go-go-related-gene) current. Linoleoylamide suppressed the amplitude of IK(IR) in a concentration-dependent manner with an IC50 value of 5 AM. Oleamide (20 AM) inhibited the amplitude of IK(IR), while neither arachidonic acid (20 AM) nor 14,15epoxyeicosatrienoic acid (20 AM) had an effect on it. In GH3 cells incubated with anandamide (20 AM) or arachidonic acid (20 AM), the linoleoylamide-induced inhibition of IK(IR) remained unaltered. In inside-out patches, arachidonic acid (20 AM) and 14,15epoxyeicosatrienoic acid (20 AM) stimulated large-conductance Ca 2+ -activated K + channels; however, linoleoylamide (20 AM) had little or no effect on them. Under current-clamp mode, linoleoylamide (20 AM) 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. D 2002 Elsevier Science B.V. All rights reserved.