Alpha 1-adrenergic receptor mediates arachidonic acid release in spinal cord neurons independent of inositol phospholipid turnover.
The alpha 1-adrenergic receptor has been shown to mediate the release of arachidonic acid in FRTL5 thyroid cells and MDCK kidney cells. In primary cultures of spinal cord cells, norepinephrine stimulated release of arachidonic acid (from neurons only) and turnover of inositol phospholipids (from neurons and glia) via alpha 1-adrenergic receptors. These two responses were dissociated by treatment with phorbol ester and pertussis toxin, which inhibited production of inositol phosphates with no appreciable effect on release of arachidonic acid. Extracellular calcium was required for release of arachidonic acid, but not for production of inositol phosphates. The calcium channel blockers nifedipine and verapamil inhibited release of arachidonic acid only. However, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), a compound that blocks intracellular calcium release, diminished production of inositol phosphates, but had little effect on release of arachidonic acid. These results suggest that alpha 1-adrenergic receptors couple to release of arachidonic acid in primary cultures of spinal cord cells by a mechanism independent of activation of phospholipase C, possibly via the activation of phospholipase A2.
Kanterman
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RY
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20892.
Felder
C C
CC
Brenneman
D E
DE
Ma
A L
AL
Fitzgerald
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S
Axelrod
J
J
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine