Synergism between A2A-adenosine receptor activation and vasoactive intestinal peptide to facilitate [3H]-acetylcholine release from the rat motor nerve terminals

The effect of vasoactive intestinal peptide (VIP) on evoked [H-3]-acetylcholine ([H-3]-ACh) release from motor nerve terminals, and its interaction with presynaptic facilitatory A(2A)-adenosine receptors was investigated in the rat phrenic nerve-hemidiaphragms. Facilitation of [H-3]-ACh release by VIP (100 nM) only becomes apparent when high frequency (50 Hz) or long lasting pulses (1 ms) were delivered to the phrenic nerve; VIP excitation was prevented by removal of endogenous adenosine tonus, with adenosine deaminase (2.5 units/ml) or with the A(2A)-receptor antagonist, 3,7-dimethyl-1-propargyl xanthine, (10 muM). Pretreatment with the selective A(2A)-receptor agonist, CGS 21680C (2 nM), potentiated the neurofacilitatory action of VIP (100 nM). The results suggest that tonic A(2A)-receptors activation by endogenous adenosine is required to trigger the facilitatory action of VIP on evoked [H-3]-ACh release from motor nerve endings. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.