Publicação
Facilitation by P2 receptor activation of acetylcholine release from rat motor nerve terminals: interaction with presynaptic nicotinic receptors
| Resumo: | 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 P2 receptor activation also modulates acetylcholine release from mature motor nerve endings.We now tested the effect of a stable ATP analogue, β,γ-Imido ATP on the nerve-evoked release of acetylcholine from adult rat hemidiaphragm preparations. β,γ-Imido ATP (10–100 µM) facilitated in a concentration-dependent manner evoked acetylcholine release, and 30 µM β,γ-Imido ATP caused a 125% facilitation of evoked acetylcholine release. This facilitatory effect of β,γ-Imido ATP (30 µM) was abolished by the P2 receptor antagonists, suramin (100 µM) and pyridoxal-phosphate-6-azophenyl-2`,4`-disulfonic acid (PPADS, 10 µM), but not by the A or A adenosine receptor antagonists, A1 or A2A 1,3-dipropyl-8-cyclopentylxanthine (50 nM) and ZM 241385 (50 nM), respectively. The facilitation of acetylcholine release by β,γ-Imido ATP (30 µM) was also prevented by the nicotinic acetylcholine receptor antagonist, D-tubocurarine (1 µM) and the facilitatory effect (40%) of the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (1 µM) was abolished by PPADS (10 µM). These results demonstrate a presynaptic facilitatory effect of P2 receptor activation at the rat phrenic nerve endings, which is tightly coupled with the presynaptic nicotinic autofacilitatory system. |
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| Autores principais: | Salgado, Audrey I. |
| Outros Autores: | Cunha, Rodrigo A.; Ribeiro, J. A. |
| Assunto: | ATP Neuromodulation Neuromuscular junction Adenosine |
| Ano: | 2000 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | 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 P2 receptor activation also modulates acetylcholine release from mature motor nerve endings.We now tested the effect of a stable ATP analogue, β,γ-Imido ATP on the nerve-evoked release of acetylcholine from adult rat hemidiaphragm preparations. β,γ-Imido ATP (10–100 µM) facilitated in a concentration-dependent manner evoked acetylcholine release, and 30 µM β,γ-Imido ATP caused a 125% facilitation of evoked acetylcholine release. This facilitatory effect of β,γ-Imido ATP (30 µM) was abolished by the P2 receptor antagonists, suramin (100 µM) and pyridoxal-phosphate-6-azophenyl-2`,4`-disulfonic acid (PPADS, 10 µM), but not by the A or A adenosine receptor antagonists, A1 or A2A 1,3-dipropyl-8-cyclopentylxanthine (50 nM) and ZM 241385 (50 nM), respectively. The facilitation of acetylcholine release by β,γ-Imido ATP (30 µM) was also prevented by the nicotinic acetylcholine receptor antagonist, D-tubocurarine (1 µM) and the facilitatory effect (40%) of the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (1 µM) was abolished by PPADS (10 µM). These results demonstrate a presynaptic facilitatory effect of P2 receptor activation at the rat phrenic nerve endings, which is tightly coupled with the presynaptic nicotinic autofacilitatory system. |
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