Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in transfected CHO cells without the concomitant administration of a Ca2+-mobilizing agent.
In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3-PPP], also induced AA release, but with somewhat lower efficacy (maximal effect: 165%; EC50=91 nM). The AA-releasing effect of dopamine was counteracted by pertussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calcium from the medium, by the phospholipase A2 (PLA2) inhibitor, quinacrine, and by long-term pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, it was antagonized by the D2 antagonists, raclopride and (-)-sulpiride--but not by (+)-sulpiride--and absent in sham-transfected CHO cells devoid of D2 receptors. The results obtained contrast to the previous notion that dopamine and other D2 receptor agonists require the concomitant administration of calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimycin), thrombin, and TRH, to influence AA release from various cell lines.
Nilsson
C L
CL
Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Sweden.
Hellstrand
M
M
Ekman
A
A
Eriksson
E
E
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D037342:Pertussis Toxin; D010880:Piperidines / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects*; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D010880:Piperidines; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000255:Adenosine Triphosphate; C026539:preclamol; D037342:Pertussis Toxin; D002118:Calcium; D004298:Dopamine