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RESEARCH PRODUCT

Adenosine negatively regulates duodenal motility in mice: role of A1 and A2A receptors

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BACKGROUND AND PURPOSE Adenosine is considered to be an important modulator of intestinal motility. This study was undertaken to investigate the role of adenosine in the modulation of contractility in the mouse duodenum and to characterize the adenosine receptor subtypes involved. EXPERIMENTAL APPROACH RT-PCR was used to investigate the expression of mRNA encoding for A1, A2A, A2B and A3 receptors. Contractile activity was examined in vitro as changes in isometric tension. KEY RESULTS In mouse duodenum, all four classes of adenosine receptors were expressed, with the A2B receptor subtype being confined to the mucosal layer. Adenosine caused relaxation of mouse longitudinal duodenal muscle; this was antagonized by the A1 receptor antagonist and mimicked by N6-cyclopentyladenosine (CPA), selective A1 agonist. The relaxation induced by A1 receptor activation was insensitive to tetrodotoxin (TTX) or Nω-nitro-l-arginine methyl ester (l-NAME). Adenosine also inhibited cholinergic contractions evoked by neural stimulation, effect reversed by the A1 receptor antagonist, but not myogenic contractions induced by carbachol. CPA and 2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride hydrate (CGS-21680), A2A receptor agonist, both inhibited the nerve-evoked cholinergic contractions. l-NAME prevented only the CGS-21680-induced effects. S-(4-Nitrobenzyl)-6-thioinosine, a nucleoside uptake inhibitor, reduced the amplitude of nerve-evoked cholinergic contractions, an effect reversed by an A2A receptor antagonist or l-NAME. CONCLUSIONS AND IMPLICATIONS Adenosine can negatively regulate mouse duodenal motility either by activating A1 inhibitory receptors located post-junctionally or controlling neurotransmitter release via A1 or A2A receptors. Both receptors are available for pharmacological recruitment, even if only A2A receptors appear to be preferentially stimulated by endogenous adenosine. LINKED ARTICLE This article is commented on by Antonioli et al., pp. 1577–1579 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01529.x