Synergism between A(2A)-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 [(3)H]-acetylcholine ([(3)H]-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 [(3)H]-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 microM). 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 [(3)H]-ACh release from motor nerve endings.
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Laboratório de Farmacologia / UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, L. Prof. Abel Salazar, 2, 4099-003 Porto, Portugal. farmacol@icbas.up.pt
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D000109:Acetylcholine / Q000493:pharmacokinetics*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003964:Diaphragm / Q000294:innervation; D004357:Drug Synergism; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D010791:Phrenic Nerve / Q000166:cytology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology*; D014316:Tritium; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D014660:Vasoactive Intestinal Peptide; C057837:3,7-dimethyl-1-propargylxanthine; D000243:Adenosine Deaminase; D000241:Adenosine; D000109:Acetylcholine; D013805:Theobromine