Both dopamine and the putative dopamine D-3 receptor antagonist PNU-99194Ainduce a biphasic inhibition of phorbol ester-stimulated arachidonic acid release from CHO cells transfected with the dopamine D-3 receptor

In Chinese hamster ovary (CHO) cells transfected with the cDNA for the dopa mine D-3 receptor, low concentrations of dopamine (IC50: 0.5 nM) counteract ed the release of arachidonic acid (AA) induced by the protein kinase C act ivator TPA (maximal inhibition: 15% at 10 - 30 nM). The effect of dopamine - which was antagonized by pretreatment with pertussis toxin (PTX) or by th e dopamine receptor antagonist haloperidol - was biphasic; thus, at increas ing concentrations of dopamine (100 nM - 1 mu M), AA levels approached base line. The preferential dopamine D-3 receptor ligand PNU-99194A displayed an effect similar to that of dopamine; thus, whereas low concentrations of PN U-99194A (IC50: 1.9 nM) reduced TPA-induced AA release (maximal inhibition: 15% at 30 - 100 nM), higher concentrations (greater than or equal to 1 mu M) were ineffective. When dopamine and PNU-99194A were administered togethe r at concentrations yielding maximal inhibition of AA release, no additive effect was observed; moreover, a high concentration of dopamine counteracte d the AA-reducing effect of a low concentration of PNU-99194A and vice vers a. It is suggested that D-3 receptors in transfected CHO cells may exert ma inly an inhibitory, but also a stimulatory influence on TPA-induced AA rele ase, and that PNU-99194A acts as an agonist in this system.