Participation of Prostaglandin E2 in Dopamine D2 Receptor‐Dependent Potentiation of Arachidonic Acid Release

Stimulation of dopamine D2 receptors potentiates Ca2+ ionophore‐ or ATP‐induced arachidonic acid (AA) release in D2 receptor cDNA‐transfected Chinese hamster ovary (CHO) cells [CHO(D2)]. By using a combination of chromatographic, biochemical, and radioimmunochemical techniques, we show here that prostaglandin (PG) E2 is a major product of AA metabolism in CHO(D2) cells stimulated with the Ca2+ ionophore A23187. Formation of this PG was markedly increased by the concomitant application of quinpirole, a D2 receptor agonist. In addition, PGE2 enhanced D2‐dependent amplification of AA release, either when it was added (EC50= 100 nM) or when it was produced endoge‐nously, as shown by experiments carried out with the cyclooxygen‐ase inhibitor indomethacin. The results suggest that PGE2 may participate in D2 receptor‐mediated potentiation of AA release in CHO(D2) cells. They also support a functional role for this PG in the modulation of dopaminergic transmission in areas of the CNS, such as amygdala and hypothalamus, where high levels of both PGE2 and dopamine D2 receptors are found.

[1]  B. Conklin,et al.  Hormonal stimulation of adenylyl cyclase through Gi-protein βγ subunits , 1992, Nature.

[2]  E. Shohami,et al.  Role of the Central Adrenergic System in the Regulation of Prostaglandin Biosynthesis in Rat Brain , 1992, Journal of neurochemistry.

[3]  Bruno Giros,et al.  Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA , 1991, Brain Research.

[4]  M. Martres,et al.  Dopamine activation of the arachidonic acid cascade as a basis for D1D2 receptor synergism , 1991, Nature.

[5]  J. Axelrod,et al.  A transduction pathway associated with receptors coupled to the inhibitory guanine nucleotide binding protein Gi that amplifies ATP-mediated arachidonic acid release. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Healy,et al.  Characterization of a dopamine receptor (DA2K) in the kidney inner medulla. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Sibley,et al.  Transfected D2 dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells. , 1991, Molecular pharmacology.

[8]  Bruno Giros,et al.  Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics , 1990, Nature.

[9]  P. Greengard,et al.  Lipoxygenase metabolites of arachidonic acid in neuronal transmembrane signalling. , 1990, Trends in pharmacological sciences.

[10]  S. Ojeda,et al.  Epoxygenase products of arachidonic acid are endogenous constituents of the hypothalamus involved in D2 receptor-mediated, dopamine-induced release of somatostatin. , 1990, Endocrinology.

[11]  J. Axelrod,et al.  Receptor-mediated activation of phospholipase A2 via GTP-binding proteins: arachidonic acid and its metabolites as second messengers , 1988, Trends in Neurosciences.

[12]  H. Morris,et al.  Platelet activating factor-mediated leukotriene biosynthesis in rat lungs: effect of prostaglandins E1 and F1a , 1987 .

[13]  P. Magistretti,et al.  Prostaglandins and the synergism between VIP and noradrenaline in the cerebral cortex , 1987, Nature.

[14]  O. Hayaishi,et al.  Involvement of GTP-regulatory protein in brain prostaglandin E2 receptor and separation of the two components. , 1986, Biochemical and biophysical research communications.

[15]  S. Narumiya,et al.  Regional Distribution of Prostaglandins D2, E2, and F2α and Related Enzymes in Postmortem Human Brain , 1984, Journal of neurochemistry.

[16]  H. Scherrer,et al.  Specific binding of [3H]prostaglandin E2 to rat brain membranes and synaptosomes , 1982, Brain Research.

[17]  J. Daly,et al.  Regulation of cyclic AMP formation in brain tissue by alpha-adrenergic receptors: requisite intermediacy of prostaglandins of the E series. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[18]  H. Morris,et al.  Interactions between second messengers: cyclic AMP and phospholipase A2- and phospholipase C-metabolites. , 1991, Life sciences.

[19]  N. Mizuno,et al.  Specific bindings of prostaglandin D2, E2 and F2 alpha in postmortem human brain. , 1985, Brain research.

[20]  R. Stehle.  [56] Physical chemistry, stability, and handling of prostaglandins E2, F2α, D2, and I2: A critical summary , 1982 .

[21]  F. Coceani,et al.  The role of prostaglandins in the central nervous system. , 1979, Annual review of physiology.

[22]  M. Muir.  Physical Chemistry , 1888, Nature.