Purinoceptor desensitization impairs but does not abolish the non-cholinergic motor transmission in rat isolated...

In order to determine the effectiveness of purinoceptor desensitization in blocking the non-cholinergic motor transmission in rat detrusor, isolated preparations of urinary bladder, pretreated with atropine 3 microM + indomethacin 10 microM were contracted by alpha, beta-methylene-ATP, a stable analogue of ATP and by electrical stimulation at frequencies of 1, 2, 4, 8 and 16 Hz. The mean maximum tension generated by alpha, beta-methylene-ATP was 43% of that by electrical field stimulation. Desensitization to the contractile action of alpha, beta-methylene-ATP was achieved by administration of alpha, beta-methylene-ATP 10 microM, three times at 10 min intervals. Responses to electrical field stimulation were reduced following induction of alpha, beta-methylene-ATP desensitization but a sizeable proportion of the response persisted (51% at 1 Hz; 29% at 8 Hz). Tetrodotoxin 0.5 microM abolished the responses to electrical field stimulation, persisting after alpha, beta-methylene-ATP desensitization. It is concluded that ATP is unlikely to be the sole non-cholinergic motor transmitter in the rat detrusor.