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Evidence that the presynaptic A2a-adenosine receptor of the rat motor nerve endings is positively coupled to adenylate cyclase

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Abstract

The action of the A2a-adenosine analogue, CGS 21680C, on electrically evoked [3H]acetylcholine ([3H]-ACh) release, and its interaction with forskolin (an activator of adenylate cyclase), MDL 12,330A (an irreversible inhibitor of adenylate cyclase), rolipram (an inhibitor of cyclic AMP specific phosphodiesterase), dibutyryl- (db-cAMP) and 8-bromo- (8-Br-cAMP) cyclic AMP analogues (substances that mimic intracellular actions of cyclic AMP), were investigated using rat phrenic nerve-hemidiaphragm preparations.

CGS 21680C facilitated [3H]ACh release. Forskolin (but not 1,9-dideoxy forskolin), rolipram, db-cAMP and 8-Br-cAMP also increased evoked neurotransmitter release in a concentration-dependent manner. When the evoked [3H]-ACh release that is dependent on stimulation of the adenylate cyclase/cyclic AMP transduction system was supramaximally stimulated by these compounds, CGS 21680 C (3 μmol/l) could not further increase [3H]-ACh release. Phosphodiesterase inhibition with low concentrations (⩽ 30 μmol/l) of rolipram significantly potentiated the augmenting effect of CGS 21680C (1 μmol/l) on evoked [3H]ACh release. MDL 12,330A (an irreversible inhibitor of adenylate cyclase) decreased evoked [3H]-ACh release. The irreversible blocking action of MDL 12,330A on [3H]-ACh release was overcome by by-passing cyclase activation with db-cAMP and 8-Br-cAMP, but could not be overcome with FSK or CGS 21680 C. The inhibitory effect of MDL 12,330A on evoked [3H]-ACh release was not mimicked by nifedipine.

It is concluded that the increase in [3H]-ACh release caused by CGS 21680C results from activation of an A2a-adenosine receptor positively linked to the adenylate cyclase/cyclic AMP system.

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Authors and Affiliations

  1. Laboratory of Pharmacology, ICBAS, University of Oporto, Portugal

    P. Correia-de-Sá & J. A. Ribeiro

  2. Laboratory of Pharmacology, Gulbenkian Institute of Science, Oeiras, Portugal

    J. A. Ribeiro

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  1. P. Correia-de-Sá
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  2. J. A. Ribeiro
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Correia-de-Sá, P., Ribeiro, J.A. Evidence that the presynaptic A2a-adenosine receptor of the rat motor nerve endings is positively coupled to adenylate cyclase. Naunyn-Schmiedeberg's Arch Pharmacol 350, 514–522 (1994). https://doi.org/10.1007/BF00173021

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  • DOI: https://doi.org/10.1007/BF00173021

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