Adenosine activating A(2A)-receptors coupled to adenylate cyclase/cyclic AMP pathway downregulates nicotinic autoreceptor function at the rat myenteric nerve terminals

Neurochemistry International
Margarida Duarte-AraújoPaulo Correia-de-Sá

Abstract

In addition to the somatodendritic region, myenteric motoneuron terminals are endowed with nicotinic autoreceptors. We aimed at investigating the effect of nicotinic receptor (nAChR) activation on [3H]-acetylcholine ([3H]-ACh) release from longitudinal muscle-myenteric plexus of the rat ileum and to evaluate whether this could be modulated by adenosine, an endogenous neuromodulator typically operating changes in intracellular cyclic AMP. The nAChR agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 1-30 microM, 3 min) increased [3H]-ACh release in a concentration-dependent manner. DMPP (30 microM)-induced [3H]-ACh outflow was attenuated by hexamethonium (0.1-1 mM), tubocurarine (1-5 microM), or by removing external Ca2+ (plus EGTA, 1 mM). In contrast to veratridine (0.2-10 microM)-induced [3H]-ACh release, the DMPP (30 microM)-induced outflow was resistant to tetrodotoxin (1 microM) and cadmium (0.5 mM). Pretreatment with adenosine deaminase (0.5 U/mL) or with the adenosine A(2A)-receptor antagonist, ZM 241385 (50 nM), enhanced nAChR-induced transmitter release. Activation of A(2A) receptors with CGS 21680C (3 nM) reduced the DMPP-induced release of [3H]-ACh. CGS 21680C (3 nM) inhibition was prevented by MDL 12,330A (10 microM, a...Continue Reading

Citations

May 28, 2009·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·C VieiraP Correia-de-Sá
Mar 28, 2006·Autonomic Neuroscience : Basic & Clinical·Paulo Correia-de-SáMargarida Duarte-Araújo
Oct 7, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Na GaoJackie D Wood
May 28, 2011·British Journal of Pharmacology·M G ZizzoR Serio
Oct 14, 2008·Pharmacology & Therapeutics·Luca AntonioliCorrado Blandizzi

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