Indications for P₂-purinoceptor subtypes in guinea pig smooth muscle

The effects of ADP, ATP, 2-methylthio ATP, α,β-methylene ADP (α,βmeADP) and α,βmeATP on smooth muscle tone and the responses to transmural nerve stimulation were studied in isolated longitudinal ileum muscle, in vas deferens and in taenia coli of the guinea pig. The nucleotides evoked contractile responses in the ileum and vas deferens preparations which were blocked by p-chloromercuribenzene sulfonic acid (PCMBS) and evoked relaxation in the taenia which was not affected by PCMBS. The potency order of the agonists in the ileum (2-methylthio ATP was more potent than ATP which was equipotent with ADP) is consistent with the suggestion that there are P_2Y receptors in the taenia. The antagonist pattern, including the inefficacy of reactive blue 2, instead suggests a similarity between the ileum receptors and the P_2X receptors in vas deferens. However, α,βmeATP did not antagonize the contractile effect of ATP in the ileum, in contrast to its effect in the vas deferens where α,βmeATP did abolish the contractile effect of ATP. The possibilities for classification of a new receptor/site of purine nucleotide action, P_2S, are considered.