期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 549, 期 2, 页码 399-408出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1113/jphysiol.2003.040410
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At synapses, ATP is released and metabolised through ecto-nucleotidases forming adenosine, which modulates neurotransmitter release through inhibitory A(1) or facilitatory A(2A) receptors, according to the amounts of extracellular adenosine. Neuromuscular junctions possess an ecto-AMP deaminase that can dissociate extracellular ATP catabolism from adenosine formation. In this study we have investigated the pattern of ATP release and its conversion into adenosine, to probe the role of ecto-AMP deaminase in controlling acetylcholine release from rat phrenic nerve terminals. Nerve-evoked ATP release was 28 +/- 12 pmol (mg tissue)(-1) at 1 Hz, 54 +/- 3 pmol (mg tissue)(-1) at 5 Hz and disproportionally higher at 50 Hz (324 +/- 23 pmol (mg tissue)(-1)). Extracellular ATP (30 mum) was metabolised with a half time of 8 2 min, being converted into ADP then into AMP. AMP was either dephosphorylated into adenosine by ecto-5'-nucleotidase (inhibited by ATP and blocked by 200 mum alpha,beta-methylene ADP) or deaminated into IMP by ecto-AMP deaminase (inhibited by 200 mum deoxycoformycin, which increased adenosine formation). Dephosphorylation and deamination pathways also catabolised endogenously released adenine nucleotides, since the nerve-evoked extracellular AMP accumulation was increased by either alpha,beta-methylene ADP (200 mum) or deoxycoformycin (200 mum). In the presence of nitrobenzylthioinosine (30 mum) to inhibit adenosine transport, deoxycoformycin (200 mum) facilitated nerve-evoked [H-3]acetylcholine release by 77 +/- 9 %, an effect prevented by the A(2A) receptor antagonist, ZM 241385 (10 nm). It is concluded that, while ecto-5'-nucleotidase is inhibited by released ATP, ecto-AMP deaminase activity transiently blunts adenosine formation, which would otherwise reach levels high enough to activate facilitatory A(2A) receptors on motor nerve terminals.
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