Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in transfected CHO cells without the concomitant administration of a Ca2+-mobilizing agent

Abstract

1. In CHO cells transfected with the rate 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). 2. 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. 3. 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.