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A study of the purinoceptors mediating contraction in the rat colon

1 The effects of a number of purine analogues were examined on the rat isolated colon muscularis mucosae. Adenosine, adenosine 5′‐monophosphate (AMP), adenosine 5′‐diphosphate (ADP), adenosine 5′‐triphosphate (ATP), 2‐methylthioATP (MeSATP), adenosine 5′‐(2‐fluorodiphosphate) (ADPβF), adenosine 5′‐(β,γ‐methylene)triphosphonate (AM PPCP) and adenosine 5′‐(α,β‐methylene)triphosphonate (AMPCPP) each contracted the muscularis mucosae in the concentration range 1–100 μm. 2 MeSATP was the most potent purine agonist, with a threshold concentration for contraction of 0.05 μm and an EC50 of approximately 0.3 μm, and AMPCPP was less potent than ATP. The enantiomer of AMPPCP, l‐AMPPCP, was inactive at concentrations up to 100 μm. 3 The adenosine receptor antagonist 8‐(p‐sulphophenyl)theophylline (8‐SPT, 50 μm) produced approximately 50 fold shifts of the dose‐response curves to adenosine, AMP and AMPPCP, whereas those to ATP, MeSATP and substance P (SP) were unaffected. Intermediate shifts were observed for the dose‐response curves to ADP, AD$1βF and AMPCPP. With a lower concentration of 8‐SPT (10 μm) a dose ratio of approximately 11 was observed for the inhibition of the effects of both adenosine and AMPPCP. 4 ATP was rapidly degraded by the tissue to ADP, AMP and adenosine, AD$1βF was more slowly degraded to AMP and adenosine, and no significant degradation of AMPPCP was detected during 20 min incubation. 5 The results are consistent with the existence in the rat colon muscularis mucosae of a mixed population of purine receptors of P2Y and P1 types. The colon thus contains the first documented incidence of a P2Y‐receptor mediating contraction. The powerful inhibition by the P1‐purinoceptor antagonist 8‐SPT of the effects of AMPPCP suggests that its action in this tissue is mediated by P1‐purinoceptors, although 8‐SPT was more potent here than has previously been demonstrated.