CGS 21680 acts as an atypical partial agonist at A2 receptors on human T-leukemia cells

The NECA derivative CGS 21680 was recently introduced as a potent selective agonist at high affinity A2_a -receptors. We have found that it is inactive on cAMP accumulation in human T-leukemia cells unless forskolin is present. When forskolin (10 uM) is added it produces a cAMP accumulation with a p...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1990, Vol.52 (suppl.2), p.93-93
Main Authors: Bertil B. Fredholm, Nedret Altiok, Susanne Ahlberg, Christer Nordstedt
Format: Article
Language:Japanese
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Summary:The NECA derivative CGS 21680 was recently introduced as a potent selective agonist at high affinity A2_a -receptors. We have found that it is inactive on cAMP accumulation in human T-leukemia cells unless forskolin is present. When forskolin (10 uM) is added it produces a cAMP accumulation with a potency that is similar to NECA, but with a much lower efficacy. The effect of NECA and of CGS 21680 was antagonized by 8-p-sulphophenyl theophylline with an equal potency. NECA pretreatment caused a down-regulation of the responses to NECA and CGS 21680. Pretreatment with CGS 21680 caused a decrease in the response to CGS 21680 but not in the response to NECA. CGS 21680 did not alter the ability of NECA to activate cAMP formation either in the presence or in the absence of forskolin. The results indicate that CGS 21680 binds to, and very weakly activates, Classical A_2 receptors on human T-cells. However, despite showing partial agonist properties it did not antagonize effects of a full agonist. This indicates that the A_2 -adenylate cyclase system in these cells has unusual properties.
ISSN:0021-5198