Aim: 

ATP and, the selective P2Y agonist, adenosine 5'-O-2-thiodiphosphate (ADPbS) induces contractile responses in the longitudinal muscle of mouse distal colon, partly involving cholinergic mechanisms. This study analyzed the noncholinergic postjunctional responses to purines, investigating the nature of the P2Y receptor subtype(s) involved and the mechanisms leading to the intracellular Ca²⁺-concentration increase necessary to trigger the muscular contraction.

Methods: 

Contractile responses of mouse colonic longitudinal muscle to P2Y receptor agonists were examined in vitro as changes in isometric tension in different experimental conditions.

Results: 

ATP (1 mM) or ADPbS (100 mM) induced muscular contraction, which was not antagonized by the selective antagonists of P2Y₁, P2Y_11,P2Y₁₂ or P2Y₁₃ receptors. Responses to maximally effective concentrationsof ATP and ADPbS were not fully additive. Each purinergic agonist induced desensitization of the response to the other agonist. Purinergic response was not modified in Ca²⁺-free medium, or in the presence of the Ca²⁺-channel blocker, nifedipine, but was virtually abolished after depletion of intracellular calcium stores. Neomycin, phospholipase C inhibitor, or 2-aminoethoxy-diphenylborate (2-APB), membrane-permeant IP₃ receptor inhibitor reduced only the response to ATP, whilst ryanodine, inhibitor of Ca²⁺ release from ryanodine-sensitive stores, abolished the response to ADPbS, without affecting that to ATP.

Conclusions: 

Taken together, our results indicate that in the murine colonic longitudinal muscle ATP and ADPbS would induce muscular contraction via a unique P2Y receptor, which recruits differential signal pathways leading to intracellular Ca²⁺ increase. The P2Y receptor involved in the ATP and ADPbS excitatory effects does not correspond to any of the known P2Y subtypes and it remains to be determined.