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 GH(3) cells were investigated. Hyperpolarization-elicited K(+) currents in GH(3) cells bathed in a high-K(+), Ca(2+)-free solution were studied to determine the effects of linoleoylamide and other related compounds on the I(K(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 I(K(IR)) in a concentration-dependent manner with an IC(50) value of 5 microM. Oleamide (20 microM) inhibited the amplitude of I(K(IR)), while neither arachidonic acid (20 microM) nor 14,15-epoxyeicosatrienoic acid (20 microM) had an effect on it. In GH(3) cells incubated with anandamide (20 microM) or arachidonic acid (20 microM), the linoleoylamide-induced inhibition of I(K(IR)) remained unaltered. In inside-out patches, arachidonic acid (20 microM) and 14,15-epoxyeicosatrienoic acid (20 microM) stimulated large-conductance Ca(2+)-activated K(+) channels; however, linoleoylamide (20 microM) had little or no effect on them. Under current-clamp mode, linoleoylamide (20 microM) increased the firing rate. In IMR-32 neuroblastoma cells, linoleoylamide also suppressed I(K(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.