The actions of adenosine and some analogues on evoked and potassium stimulated release at skeletal and autonomic neuromuscular junctions

Abstract

The actions of the nucleosides adenosine, 1-methyladenosine, 1-methylisoguanosine and 2-chloradenosine on transmitter release at the mammalian neuromuscular junction and the vas deferens have been examined. All the nucleosides depressed the evoked release of acetylcholine at the neuromuscular junction, the order of potency being 2-chloroadenosine greater than 1-methylisoguanosine greater than 1-methyladenosine much greater than adenosine. This correlated reasonably with the potency of these compounds in depressing spinal reflexes in anaesthetized mice (Buckle and Spence 1981). Neither adenosine (0.5 and 1.0 mmol l-1) or 1-methylisoguanosine (10 and 20 mumol l-1) had any effect on the elevation of minature endplate potential frequency caused by 12 mmol l-1 K+ at the neuromuscular junction. In the guinea-pig vas deferens, however, 1-methylisoguanosine and adenosine were approximately equipotent in depressing overflow of radioactively labelled noradrenaline. The actions of the nucleosides have been compared with their effects on adenylate cyclase and their ability to resist uptake and deamination. It is concluded that the relative potencies of the nucleosides are not determined solely by their ability to survive in the extracellular fluid.