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Reciprocal interactions between adenosine A2A and dopamine D2 receptors in Chinese hamster ovary cells co-transfected with the two receptors

In English

Författare

  • B Kull
  • S Ferre
  • G Arslan
  • P Svenningsson
  • K Fuxe
  • Christer Owman
  • B B Fredholm

Summary, in English

Human adenosine A2A and rat dopamine D2 receptors (A2A and D2 receptors) were co-transfected in Chinese hamster ovary (CHO) cells to study the interactions between two receptors that are co-localized in striatopallidal gamma-aminobutyric acid-(GABA)ergic neurons. Membranes from transfected cells showed a high density of D2 (3.6 pmol per mg protein) and A2A receptors (0.56 pmol per mg protein). The D2 receptors were functional: an agonist, quinpirole, could stimulate GTPgammaS binding and reduce stimulated adenylyl cyclase activity. The A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) decreased high-affinity binding of the agonist dopamine at D2 receptors. Activation of adenosine A2A receptors shifted the dose-response curve for quinpirole on adenosine 3',5'-cyclic monophosphate (cAMP) to the right. However, CGS 21680 did not affect dopamine D2 receptor-induced GTPgammaS binding, but did cause a concentration-dependent increase in cAMP accumulation. The maximal cAMP response was decreased by the D2 agonist quinpirole in a concentration-dependent manner, but there was no change in EC50 and no effect in cells transfected only with adenosine A2A receptors. A2A receptor activation also increased phosphorylation of cAMP response element-binding protein and expression of c-fos mRNA. These effects were also strongly counteracted by quinpirole. These results show that the antagonistic actions between adenosine A2A and dopamine D2 receptors noted previously in vivo can also be observed in CHO cells where the two receptors are co-transfected. Thus, no brain cell-specific factors are required for such interactions. Furthermore, the interaction at the second messenger level and beyond may be quantitatively more important than A2A receptor-mediated inhibition of high affinity D2 agonist binding to the receptor.

Avdelning/ar

  • Drug Target Discovery

Publiceringsår

1999

Språk

Engelska

Sidor

1035-1045

Publikation/Tidskrift/Serie

Biochemical Pharmacology

Volym

58

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Pharmacology and Toxicology

Nyckelord

  • adenosine A2A receptors
  • dopamine D2 receptors
  • receptor interaction
  • CHO cells
  • G-proteins
  • transfection
  • receptor binding
  • cyclic AMP

Status

Published

Forskningsgrupp

  • Drug Target Discovery

ISBN/ISSN/Övrigt

  • ISSN: 0006-2952