Relationship of metabolism of 2?-, 3?- and 5?-adenine nucleotides to presynaptic inhibition of transmitter release in rat vas deferens

Abstract

In the isolated rat vas deferens stimulated at 0.2 Hz, a series of 2′, 3′-, and 5′-substituted adenine nucleotides all inhibited the twitch responses, their actions being potentiated by the nucleoside transport inhibitors, HNBTGR, NBMPR and dipyridamole. The metabolism of these nucleotides was examined utilising HPLC analysis of the bathing medium after exposure to 30 μM nucleoside or nucleotide for 5 min. 5′-AMP, 5′-ADP, 5′-ATP, and NAD⁺ were all partially hydrolysed to adenosine, the relative extent of this being 5′-AMP>5′-ADP=5′-ATP≫NAD⁺. However, the other nucleotides examined were not detectably converted to adenosine or to adenosine deamination products. These results indicate that the 2′-, 3′- and 5′-substituted nucleotides studied act at a P₁-purinoceptor in rat vas deferens to inhibit neurotransmission and, with the exception of 5′-AMP, 5′-ADP, 5′-ATP and NAD⁺, all appear to act directly at this receptor. However, the 5′-adenine nucleotides (AMP, ADP and ATP) and NAD⁺ all appear to act at least partially indirectly subsequent to their hydrolysis to adenosine.