Modulation by adenosine of both muscarinic M-1-facilitation and M-2-inhibition of [H-3]-acetylcholine release from the rat motor nerve terminals

• Tipo: Artigo em Revista Científica Internacional
• Data: 2002

Autores

oliveira, l (Autor) Outra; Timoteo, MA (Autor) Outra; Paulo Correia de Sá (Autor) ICBAS

Revista

Título: European Journal of Neuroscience

Vol. 15

Páginas: 1728-1736

ISSN: 0953-816X

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 54 Citações

Scopus - 63 Citações

Outras Informações

ID Authenticus: P-000-P4C

DOI: 10.1046/j.1460-9568.2002.02020.x

Abstract (EN): The crosstalk between adenosine and muscarinic autoreceptors regulating evoked [(3) H]-acetylcholine ([(3) H]-ACh) release was investigated on rat phrenic nerve-hemidiaphragm preparations. Motor nerve terminals possess facilitatory M-1 and inhibitory M-2 autoreceptors that can be activated by McN-A-343 (1-30 mum) and oxotremorine (0.3-100 mum), respectively. The muscarinic receptor antagonist, dicyclomine (3 nm-10 mum), caused a biphasic (inhibitory/facilitatory) effect, indicating that M-1 -facilitation prevails during 5 Hz stimulation trains. Concomitant activation of AF-DX 116-sensitive M-2 receptors was partially attenuated, as pretreatment with M-1 antagonists, muscarinic toxin 7 (MT-7, 0.1 nm) and pirenzepine (1 nm), significantly enhanced inhibition by oxotremorine. Activation of A(2A) -adenosine receptors with CGS 21680C (2 nm) (i) potentiated oxotremorine inhibition, and (ii) shifted McN-A-343-induced facilitation into a small inhibitory effect. Conversely, the A(1) -receptor agonist, R-N (6) -phenylisopropyl adenosine (R-PIA, 100 nm), attenuated the inhibitory effect of oxotremorine, without changing facilitation by McN-A-343. Synergism between A(2A) and M-2 receptors is regulated by a reciprocal interaction with facilitatory M-1 receptors, which may be prevented by pirenzepine (1 nm). During 50 Hz-bursts, facilitation (M-1 ) of [(3) H]-ACh release by McN-A-343 disappeared, while the inhibitory (M-2 ) effect of oxotremorine became predominant. This muscarinic shift results from the interplay with A(2A) receptors, as it was precluded by the selective A(2A) receptor antagonist, ZM 241385 (10 nm). In conclusion, when the muscarinic M-1 positive feedback loop is fully operative, negative regulation of ACh release is mediated by adenosine A(1) receptors. During high frequency bursts, tonic activation of A(2A) receptors promotes M-2 autoinhibition by braking the M-1 receptor operated counteraction.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9