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

• Type: Article in International Scientific Journal
• Date: 2002

Authors

oliveira, l (Author) Other; Timoteo, MA (Author) Other; Paulo Correia de Sá (Author) ICBAS

Journal

Title: European Journal of Neuroscience

Vol. 15

Pages: 1728-1736

ISSN: 0953-816X

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 54 Citations

Scopus - 63 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9