Facilitation by P(2) receptor activation of acetylcholine release from rat motor nerve terminals: interaction with presynaptic nicotinic receptors.
ATP is released from motor nerve endings together with acetylcholine. Released adenine nucleotides can be extracellularly metabolized into adenosine, which is a presynaptic neuromodulator at neuromuscular junctions, but it is not known if P(2) receptor activation also modulates acetylcholine release from mature motor nerve endings. We now tested the effect of a stable ATP analogue, beta,gamma-imido ATP on the nerve-evoked release of acetylcholine from adult rat hemidiaphragm preparations. beta,gamma-Imido ATP (10-100 microM) facilitated in a concentration-dependent manner evoked acetylcholine release, and 30 microM beta,gamma-imido ATP caused a 125% facilitation of evoked acetylcholine release. This facilitatory effect of beta,gamma-imido ATP (30 microM) was abolished by the P(2) receptor antagonists, suramin (100 microM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 microM), but not by the A(1) or A(2A) adenosine receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (50 nM) and ZM 241385 (50 nM), respectively. The facilitation of acetylcholine release by beta, gamma-imido ATP (30 microM) was also prevented by the nicotinic acetylcholine receptor antagonist, D-tubocurarine (1 microM) and the facilitatory effect (40%) of the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (1 microM) was abolished by PPADS (10 microM). These results demonstrate a presynaptic facilitatory effect of P(2) receptor activation at the rat phrenic nerve endings, which is tightly coupled with the presynaptic nicotinic autofacilitatory system.
Salgado
A I
AI
Laboratory of Neurosciences, Faculty of Medicine, Lisbon, Portugal.
Cunha
R A
RA
Ribeiro
J A
JA
D000109:Acetylcholine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism
D011978:Receptors, Nicotinic; D018048:Receptors, Purinergic P2; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D000109:Acetylcholine