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Activation of Adensine A 1 and A 2A Receptors Modulates Dopamine D 2 Receptor‐Induced Responses in Stably Transfected Human Neuroblastoma Cells
Author(s) -
Salim Hassan,
Ferré Sergi,
Dalal Abderrahim,
Peterfreund Robert A.,
Fuxe Kjell,
Vincent JeanDidier,
Lledo PierreMarie
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0740432.x
Subject(s) - adenosine , receptor , adenosine a2b receptor , agonist , dopamine receptor , medicine , endocrinology , adenosine receptor , dopamine , adenosine a1 receptor , dopaminergic , adenosine a3 receptor , biology , endogenous agonist , chemistry , dopamine receptor d1 , biochemistry
Adenosine can influence dopaminergic neuro‐transmission in the basal ganglia via postsynaptic inter‐action between adenosine A 2A and dopamine D 2 receptors. We have used a human neuroblastoma cell line (SH‐SY5Y) that was found to express constitutively moderate levels of adenosine A 1 and A 2A receptors (∼100 fmol/mg of protein) to investigate the interactions of A 2A /D 2 receptors, at a cellular level. After transfection with human D 2L receptor cDNA, SH‐SY5Y cells expressed between 500 and 1,100 fmol of D 2 receptors/mg of protein. In membrane preparations, stimulation of adenosine A 2A receptors decreased the affinity of dopamine D 2 receptors for dopamine. In intact cells, the calcium concentration elevation induced by KCl treatment was moderate, and dopamine had no effect on either resting intracellular free Ca 2+ concentration ([Ca 2+ ] i ) or KCl‐induced responses. In contrast, pretreatment with adenosine deaminase for 2 days dramatically increased the elevation of [Ca 2+ ] i evoked by KCl, which then was totally reversed by dopamine. The effects induced by 48‐h adenosine inactivation were mimicked by application of adenosine A 1 antagonists and could not be further reversed by acute activation of either A 1 or A 2A receptors. Acute application of the selective A 2 receptor agonist CGS‐21680 counteracted the D 2 receptor‐induced [Ca 2+ ] i responses. The present study shows that SH‐SY5Y cells are endowed with functional adenosine A 2A and A 1 receptors and that A 2A receptors exert an antagonistic acute effect on dopamine D 2 receptor‐mediated functions. In contrast, A 1 receptors induce a tonic modulatory role on these dopamine functions.