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 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).

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.

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