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: Yen Chin Liu, Sheng Nan Wu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 458 Issue 1-2 Pg. 37-47 (Jan 01 2003) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12498905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Arachidonic Acids
• Calcium Channels, L-Type
• Endocannabinoids
• Hydantoins
• Imidazoles
• Imidazolidines
• Linoleic Acids
• Piperazines
• Piperidines
• Polyunsaturated Alkamides
• Potassium Channels
• Pyridines
• linoleoylamide
• alpha-Linolenic Acid
• E 4031
• Arachidonic Acid
• azimilide
• 14,15-epoxy-5,8,11-eicosatrienoic acid
• 8,11,14-Eicosatrienoic Acid
• Calcium
• anandamide

Topics

• 8,11,14-Eicosatrienoic Acid (analogs & derivatives, pharmacology)
• Amides (chemistry, pharmacology)
• Animals
• Arachidonic Acid (pharmacology)
• Arachidonic Acids (pharmacology)
• Calcium (pharmacology)
• Calcium Channels, L-Type (physiology)
• Dose-Response Relationship, Drug
• Endocannabinoids
• Humans
• Hydantoins
• Imidazoles (pharmacology)
• Imidazolidines
• Infant, Newborn
• Linoleic Acids (pharmacology)
• Membrane Potentials (drug effects)
• Neuroblastoma (pathology, physiopathology)
• Patch-Clamp Techniques
• Piperazines (pharmacology)
• Piperidines (pharmacology)
• Pituitary Neoplasms (pathology, physiopathology)
• Polyunsaturated Alkamides
• Potassium Channels (physiology)
• Pyridines (pharmacology)
• Tumor Cells, Cultured (drug effects)
• alpha-Linolenic Acid (chemistry, pharmacology)