EVIDENCE THAT THE PRESYNAPTIC A(2A)-ADENOSINE RECEPTOR OF THE RAT MOTOR-NERVE ENDINGS IS POSITIVELY COUPLED TO ADENYLATE-CYCLASE

• Type: Article in International Scientific Journal
• Date: 1994

Authors

Paulo Correia de Sá (Author) Other; RIBEIRO, JA (Author) Other

Journal

Title: Naunyn-Schmiedeberg's Archives of Pharmacology

Vol. 350

Pages: 514-522

ISSN: 0028-1298

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 38 Citations

Scopus - 41 Citations

Other information

Authenticus ID: P-001-JDX

DOI: 10.1007/bf00173021

Abstract (EN): The action of the A(2a)-adenosine analogue, CGS 21680C, on electrically evoked [H-3]acetylcholine ([H-3]-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 [H-3]-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 [H-3]-ACh release that is dependent on stimulation of the adenylate cyclase/cyclic AMP transduction system was supramaximally stimulated by these compounds, CGS 21680C (3 nmol/l) could not further increase [H-3]-ACh release. Phosphodiesterase inhibition with low concentrations (less than or equal to 30 mu mol/l) of rolipram significantly potentiated the augmenting effect of CGS 21680C (1 nmol/l) on evoked [H-3]-ACh release. MDL 12,330A (an irreversible inhibitor of adenylate cyclase) decreased evoked [H-3]-ACh release. The irreversible blocking action of MDL 12,330A on [H-3]-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 21680C. The inhibitory effect of MDL 12,330A on evoked [H-3]-ACh release was not mimicked by nifedipine. It is concluded that the increase in [H-3]-ACh release caused by CGS 21680C results from activation of an A(2a)-adenosine receptor positively linked to the adenylate cyclase/cyclic AMP system.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9