Aim: 

There is evidence that suggests a complex role for adenosine in the regulation of gastrointestinal (GI) motor functions under normal or pathological conditions. In mice, important models for investigating GI motility, a full description of the function as well as of the distribution of adenosine receptors (A₁, A₂ and A₃ receptor subtypes) in the different regions of the GI tract, is not yet available. We aimed to investigate the role of adenosine in the modulation of the spontaneous contractile activity in mouse duodenum longitudinal muscle and to characterize the adenosine receptor subtypes involved and the related transduction mechanisms.

Methods: 

Mechanical responses to exogenous adenosine were assessed on longitudinally oriented duodenal segments, suspended in an organ bath and the expression of mRNA for adenosine receptors was evaluated by RT-PCR.

Results: 

A transcript of all the adenosine receptors was found in whole thickness duodenum. Functional evidence indicated that adenosine produced a concentration-dependent relaxation of mouse duodenum markedly reduced by DPCPX, A₁ receptor antagonist, but not affected by DMPX or MRS 1220, A₂ and A₃ receptor antagonists respectively. Neither tetrodotoxin, neuronal blocker, nor L-NAME, nitric oxide synthase blocker, modified the adenosine responses. The relaxation was significantly antagonized in the presence of cyclopiazonic acid, a specific inhibitor of the sarcoplasmic reticulum (SR) Ca²⁺-ATPase, or in the presence of TEA, a K⁺ channels blocker.

Conclusion: 

adenosine relaxes mouse duodenal longitudinal smooth muscle via A₁ receptor activation without an involvement of neuronal action potential or NO synthesis. Functional SR Ca²⁺-ATPase and increase of potassium conductances are essential requirements for adenosine to regulate contractile activity.