Clonidine-evoked selective P1-purinoceptor antagonism of contraction of guinea-pig urinary bladder.

The effect of clonidine on P1- and P2-purinoceptors of guinea-pig urinary bladder was compared to that of alpha, beta-methylene ATP, a selective P2-purinoceptor desensitizer. After, alpha, beta-methylene ATP, 10 microM, vesical contraction produced by ATP was eliminated while that caused by acetylcholine was unaffected. Clonidine, however, failed to antagonize ATP-induced contraction of the segment even at 100 microM. Electrically evoked contraction of the bladder was partly attenuated by 0.3 microM atropine and the remainder was markedly reduced by 3-30 microM alpha, beta-methylene ATP, suggesting an important role of ATP as an excitatory transmitter in this tissue. This stimulus-evoked contraction was also suppressed by adenosine, a P1-purinoceptor agonist, in a concentration-dependent fashion, and the suppression was greatly antagonized by 50 microM clonidine. These results suggest that the antagonistic property of clonidine is substantially selective for presynaptic P1-purinoceptors in contrast with that of alpha, beta-methylene ATP for postsynaptic P2-purinoceptors.