Dopamine D2 receptor-induced COX-2-mediated production of prostaglandin E2 in D2-transfected Chinese hamster ovary cells without simultaneous administration of a Ca2+-mobilizing agent

We have earlier demonstrated that dopamine stimulates the liberation of the prostaglandin E-2 (PGE(2)) precursor, arachidonic acid, in Chinese hamster ovary cells transfected with the rat dopamine D-2 receptor (long isoform), also without concomitant administration of a Ca2+-releasing agent [Nilsson et al., Br J Pharmacol 1998;124:1651-8]. In the present report, we show that dopamine, under the same conditions, also induces a concentration-dependent increase in the production of PGE(2), with a maximal effect of 235% at similar to100 muM, and with an EC50 of 794 nM. The effect was counteracted by the D2 antagonist eticlopride, pertussis toxin, the inhibitor of intracellular Ca2+ release TMB-8, incubation in Ca2+-free experimental medium, and PKC desensitization obtained by chronic pretreatment with the phorbol ester TPA. It was also antagonized by the non-specific cyclooxygenase (COX) inhibitor, indomethacin, and by the selective COX-2 inhibitor, NS-398, but not by the specific COX-1 inhibitor, valeryl salicylate. Both the non-specific phospholipase A(2) inhibitor, quinacrine, and an inhibitor of cPLA(2) and iPLA(2), AACOF3, counteracted the effect; in contrast, a selective iPLA(2), inhibitor, BEL, and a selective sPLA(2) inhibitor, TAPC, were ineffective. No effects of dopamine were obtained in control cells mock-transfected with the p3C vector only. The results reinforce previous assumptions that dopamine may interact with eicosanoid metabolism by means of D-2 receptor activation, and implicate an involvement of cPLA(2) and COX-2 in this effect. It is suggested that measurement of dopamine-induced PGE(2) production may serve as a convenient way to study D-2 receptor function in vitro. (C) 2002 Elsevier Science Inc. All rights reserved.