title: Block of erg current by linoleoylamide, a sleep-inducing agent, in pituitary GH3 cells.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.
authors.forename: Yen Chin
authors.initials: YC
authors.lastname: Liu
authors.forename: Sheng Nan
authors.initials: SN
authors.lastname: Wu
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D006801:Humans; D006827:Hydantoins; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007231:Infant, Newborn; D008041:Linoleic Acids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000473:pathology / Q000503:physiopathology; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D017962:alpha-Linolenic Acid / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D020746:Calcium Channels, L-Type; D063388:Endocannabinoids; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D008041:Linoleic Acids; D010879:Piperazines; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D011725:Pyridines; C473834:linoleoylamide; D017962:alpha-Linolenic Acid; C063968:E 4031; D016718:Arachidonic Acid; C086123:azimilide; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D002118:Calcium; C078814:anandamide