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.
Liu
Yen Chin
YC
Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.
Wu
Sheng Nan
SN
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*
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