title: 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.
abstract: 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.
authors: Department of Pharmacology, Institute of Physiology and Pharmacology, Göteborg University, Sweden. neuroendo@pharm.gu.se
authors: C L
authors: CL
authors: Nilsson
authors: M
authors: M
authors: Hellstrand
authors: A
authors: A
authors: Ekman
authors: E
authors: E
authors: Eriksson
mesh_terms: 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
chemical_list: 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