Potentiating and inhibitory effects of periodate-oxidized ATP analogs on contractions of vas deferens to ATP

Abstract

Previous studies have shown that treatment of guinea-pig isolated vas deferens with the affinity label periodate-oxidized ATP (2',3'-dialdehyde ATP), results in two irreversible effects on biphasic contractile responses to ATP, i.e., potentiation of the P2X purinoceptor-mediated first phase and inhibition of the ecto-kinase-mediated second phase. The present experiments were designed to evaluate whether periodate-oxidized ADP, periodate-oxidized AMP, and periodate-oxidized adenosine, produce similar effects. Periodate-oxidized ATP and periodate-oxidized ADP (10(-2) M) elicited contraction of the vas deferens (periodate-oxidized ATP > periodate-oxidized ADP; periodate-oxidized AMP and periodate-oxidized adenosine had no agonist activity. After incubation of the preparations for 5 min with 10(-2) M periodate-oxidized ATP, periodate-oxidized ADP, periodate-oxidized AMP or periodate-oxidized adenosine, the first phase of contraction to submaximal ATP concentrations was potentiated. Simultaneously, periodate-oxidized ATP, periodate-oxidized ADP and periodate-oxidized AMP inhibited the second contractile phase, whereas periodate-oxidized adenosine did not. The results indicate that the requirement for 5'-phosphate to produce potentiation and inhibition is different: 5'-phosphate is not needed to potentiate the first phase of contraction to ATP, but at least one 5'-phosphate is required to inhibit the second phase of contraction.