Aim: 

The aim of this study was to analyze, in the longitudinal muscle of mouse ileum, the subtypes of P1 purinergic receptors involved in the adenosine-induced inhibition of the contractility and the coupled action mechanisms.

Methods: 

Mechanical responses to exogenous adenosine on the ileal longitudinal muscle was assessed, in vitro, as changes in isometric tension and the expression of adenosine receptors was evaluated by Western blotting analysis.

Results: 

Adenosine (1 mM–1 mM) caused tetrodotoxin-insensitive and concentration-dependent inhibitory effects consisting in a reduction of the spontaneous contraction amplitude of mouse ileal longitudinal muscle up to their complete disappearance. Teophylline, non selective P1 receptor antagonist, or DPCPX, A₁ receptor antagonist, markedly reduced adenosine effects. On the contrary, neither DMPX nor MRS 1220, A₂ and A₃ receptor antagonists respectively, modified adenosine effects. A₁ receptor expression was detected in mouse ileum with higher levels in the smooth muscle. Among different K⁺ channel blockers tested, only TEA, non-selective inhibitor of voltage gated potassium channels and large-conductance Ca²⁺-activated potassium channel (BK_Ca), and iberiotoxin, selective BK_Ca channel blocker, significantly reduced adenosine-induced inhibitory effects. However, the combination of iberiotoxin plus apamin, small conductance Ca²⁺-dependent K⁺ channels (SK_Ca) blocker, caused a reduction of the adenosine inhibitory effect greater than iberiotoxin alone.

Conclusions: 

Exogenous adenosine acts as inhibitory modulator of the contractility of mouse ileal longitudinal smooth muscle via a mechanism not dependent on neuronal action potential and involving exclusively A₁ receptors. A1 receptors activation would induce opening of potassium channels that share characteristics between BK_Ca and SK_Ca channels.