Both dopamine and the putative dopamine D3 receptor antagonist PNU-99194A induce a biphasic inhibition of phorbol ester-stimulated arachidonic acid release from CHO cells transfected with the dopamine D3 receptor.
In Chinese hamster ovary (CHO) cells transfected with the cDNA for the dopamine D3 receptor, low concentrations of dopamine (IC50: 0.5 nM) counteracted the release of arachidonic acid (AA) induced by the protein kinase C activator TPA (maximal inhibition: 15% at 10 - 30 nM). The effect of dopamine -- which was antagonized by pretreatment with pertussis toxin (PTX) or by the dopamine receptor antagonist haloperidol -- was biphasic; thus, at increasing concentrations of dopamine (100 nM - 1 microM), AA levels approached baseline. The preferential dopamine D3 receptor ligand PNU-99194A displayed an effect similar to that of dopamine; thus, whereas low concentrations of PNU-99194A (IC50: 1.9 nM) reduced TPA-induced AA release (maximal inhibition: 15% at 30 - 100 nM), higher concentrations (> or =1 microM) were ineffective. When dopamine and PNU-99194A were administered together at concentrations yielding maximal inhibition of AA release, no additive effect was observed; moreover, a high concentration of dopamine counteracted the AA-reducing effect of a low concentration of PNU-99194A and vice versa. It is suggested that D3 receptors in transfected CHO cells may exert mainly an inhibitory, but also a stimulatory influence on TPA-induced AA release, and that PNU-99194A acts as an agonist in this system.
Nilsson
C L
CL
Department of Pharmacology, Institute of Physiology and Pharmacology, Göteborg University, Sweden. neuroendo@pharm.gu.se
Hellstrand
M
M
Ekman
A
A
Eriksson
E
E
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D007189:Indans / Q000494:pharmacology*; D037342:Pertussis Toxin; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000502:physiology*; D050637:Receptors, Dopamine D3; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007189:Indans; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D010566:Virulence Factors, Bordetella; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; D016718:Arachidonic Acid; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine