DIRECT DOPAMINE D-2-RECEPTOR-MEDIATED MODULATION OF ARACHIDONIC-ACID RELEASE IN TRANSFECTED CHO CELLS WITHOUT THE CONCOMITANT ADMINISTRATION OF A CA2-MOBILIZING AGENT()

1 In CHO cells transfected with the rat dopamine D-2 receptor (long is oform), administration of dopamine per se elicited a concentration-dep endent increase in arachidonic acid (AA) release. The maximal effect w as 197% of controls (EC50=25 nM). The partial D-2 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 pert ussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N-di ethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calciu m from the medium, by the phospholipase A(2) (PLA(2)) inhibitor, quina crine, and by long-term pretreatment with the phorbol ester, 12-O-tetr adecanoylphorbol-13-acetate (TPA). In addition,it was antagonized by t he D-2 antagonists, raclopride and (-)-sulpiride-but not by (+)-sulpir ide-and absent in sham-transfected CHO cells devoid of D-2 receptors. 3 The results obtained contrast to the previous notion that dopamine a nd other D-2 receptor agonists require the concomitant administration of calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimyci n), thrombin, and TRH, to influence AA release from various cell lines .