Transfected D2 dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells.
A rat D2L dopamine receptor, a splice variant of the D2 receptor, has recently been cloned. When transfected into and stably expressed in Chinese hamster ovary cells, these receptors mediate the inhibition of both basal and forskolin-stimulated cAMP production, as previously described. We examined what role this receptor might play in the production of the second messenger arachidonic acid. The calcium ionophore A23187 stimulated the release of arachidonic acid, and this release of arachidonic acid was potentiated by dopamine in a concentration-dependent manner. Dopamine alone, however, had no effect on arachidonic acid release. Quinpirole, a D2-selective agonist, augmented A23187-stimulated arachidonic acid release, and sulpiride, a D2-selective antagonist, blocked this augmentation. cAMP analogs and agents that activate adenylyl cyclase were utilized in an attempt to overcome this dopamine effect. Forskolin, prostaglandin E2, dibutyryl-cAMP, 8-(4-chlorophenylthio)-cAMP, and pertussis toxin all had no appreciable effect on either A23187-stimulated arachidonic acid release or the dopamine enhancement. Inhibition of protein kinase C using long term phorbol ester desensitization and pharmacological inhibitors diminished the dopamine potentiation of arachidonic acid release. These results suggest that the D2 receptor may be increasing the release of arachidonic acid by a mechanism involving protein kinase C but independent of the D2 receptor's inhibition of adenylyl cyclase.
Kanterman
R Y
RY
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892.
Mahan
L C
LC
Briley
E M
EM
Monsma
F J
FJ
Sibley
D R
DR
Axelrod
J
J
Felder
C C
CC
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004357:Drug Synergism; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008555:Melitten / Q000494:pharmacology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D001095:Arachidonic Acids; D004873:Ergolines; D011954:Receptors, Dopamine; D010566:Virulence Factors, Bordetella; D008555:Melitten; D019257:Quinpirole; D016718:Arachidonic Acid; D000001:Calcimycin; D013469:Sulpiride; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D006220:Haloperidol; D001058:Apomorphine; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine