La maladie de Parkinson en France (serveur d'exploration)

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Autocrine activation of adenosine A1 receptors blocks D1A but not D1B dopamine receptor desensitization

Identifieur interne : 003A84 ( Main/Merge ); précédent : 003A83; suivant : 003A85

Autocrine activation of adenosine A1 receptors blocks D1A but not D1B dopamine receptor desensitization

Auteurs : Stéphane Le Crom [France] ; Delphine Prou [France] ; Philippe Vernier [France]

Source :

RBID : Pascal:03-0111566

Descripteurs français

English descriptors

Abstract

Adenosine is known to modulate dopamine responses in several brain areas. Here, we show that tonic activation of adenosine receptors is able to impede desensitization of D1 dopamine receptors. As measured by cAMP accumulation in transfected COS-7 cells, long-term exposure to dopamine agonists promoted desensitization of D1B receptor but not that of D1A receptor. The inability of D1A receptor to desensitize was a result of the adenosine present in culture medium acting through activation of adenosine A1 receptors. Cell incubation with either adenosine deaminase, CGS-15943, a generic adenosine receptor antagonist, or the A1 antagonist DPCPX restored the long-term desensitization time-course of D1A receptors. In Ltk cells stably expressing A1 adenosine receptors and D1A dopamine receptors, pre-treatment of cells with R(-)-PIA, a full A1 receptor agonist, did not significantly inhibit the acute increase in cAMP levels induced by D1 receptor agonists, but blocked desensitization of D1A receptors. However, simultaneous activation of A1 and D1A receptors promoted a delayed D1A receptor desensitization. This suggests that functional interaction between A1 and D1A receptors may depend on the activation kinetics of components regulating D1 receptor responses, acting differentially on D1A and D1B receptors.

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Pascal:03-0111566

Le document en format XML

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<term>D1 Dopamine receptor</term>
<term>D5 dopamine receptor</term>
<term>Desensitization</term>
<term>Dopamine</term>
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<term>Dopamine</term>
<term>Interaction</term>
<term>Récepteur dopaminergique D5</term>
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<term>Parkinson maladie</term>
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<front>
<div type="abstract" xml:lang="en">Adenosine is known to modulate dopamine responses in several brain areas. Here, we show that tonic activation of adenosine receptors is able to impede desensitization of D
<sub>1</sub>
dopamine receptors. As measured by cAMP accumulation in transfected COS-7 cells, long-term exposure to dopamine agonists promoted desensitization of D
<sub>1B</sub>
receptor but not that of D
<sub>1A</sub>
receptor. The inability of D
<sub>1A</sub>
receptor to desensitize was a result of the adenosine present in culture medium acting through activation of adenosine A1 receptors. Cell incubation with either adenosine deaminase, CGS-15943, a generic adenosine receptor antagonist, or the A
<sub>1</sub>
antagonist DPCPX restored the long-term desensitization time-course of D
<sub>1A</sub>
receptors. In Ltk cells stably expressing A1 adenosine receptors and D
<sub>1A</sub>
dopamine receptors, pre-treatment of cells with R(-)-PIA, a full A1 receptor agonist, did not significantly inhibit the acute increase in cAMP levels induced by D1 receptor agonists, but blocked desensitization of D
<sub>1A</sub>
receptors. However, simultaneous activation of A
<sub>1</sub>
and D
<sub>1A</sub>
receptors promoted a delayed D
<sub>1A</sub>
receptor desensitization. This suggests that functional interaction between A1 and D
<sub>1A</sub>
receptors may depend on the activation kinetics of components regulating D1 receptor responses, acting differentially on D
<sub>1A</sub>
and D
<sub>1B</sub>
receptors.</div>
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