Negative crosstalk between M-1 and M-2 muscarinic autoreceptors involves endogenous adenosine activating A(1) receptors at the rat motor endplate

• Type: Article in International Scientific Journal
• Date: 2009

Authors

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

Journal

Title: Neuroscience Letters

Vol. 459

Pages: 127-131

ISSN: 0304-3940

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 32 Citations

Scopus - 30 Citations

Other information

Authenticus ID: P-003-GS0

DOI: 10.1016/j.neulet.2009.05.001

Abstract (EN): At the rat motor nerve terminals, activation of muscarinic M-1 receptors negatively modulates the activity of inhibitory muscarinic M-2 receptors. The present work was designed to investigate if the negative crosstalk between muscarinic M-1 and M-2 autoreceptors involved endogenous adenosine tonically activating A(1) receptors on phrenic motor nerve terminals. The experiments were performed on rat phrenic nerve-hemidiaphragm preparations loaded with [H-3]-choline (2.5 mu Ci/ml). Selective activation of muscarinic M-1 and adenosine A(1) receptors with 4-(N-[3-clorophenyl]-carbamoyloxy)-2-butyryltrimethylammonium (McN-A-343, 3 mu M) and R-N-6-phenylisopropyladenosine (R-PIA, 100 nM), respectively, significantly attenuated inhibition of evoked [H-3]-ACh release induced by muscarinic M-2 receptor activation with oxotremorine (10 mu M). Attenuation of the inhibitory effect of oxotremorine (10 mu M) by R-PIA (100nM) was detected even in the presence of pirenzepine (1 nM) blocking M-2 autoreceptors, suggesting that suppression of M-2-inhibiton by A(1) receptor activation is independent on muscarinic M-1 receptor activity. Conversely, the negative crosstalk between M-1 and M-2 autoreceptors; seems to involve endogenous adenosine tonically activating A(1) receptors. This was suggested, since attenuation of the inhibitory effect of oxotremorine (10 mu M) by McN-A-343 (3 mu M) was suppressed by the A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (2.5 nM), and by reducing extracellular adenosine with adenosine deaminase (0.5 U/mL) or with the adenosine transport blocker, S-(p-nitrobenzyl)-6-thioinosine (NBTI, 10 mu M). The results suggest that the negative crosstalk between muscarinic M-1 and M-2 autoreceptors involves endogenous adenosine outflow via NBTI-sensitive (es) nucleoside transport system channelling to the activation of presynaptic inhibitory A, receptors at the rat motor endplate.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5