ATP and phosphate-modified adenine nucleotide analogues. Effects on insulin secretion and calcium uptake.

Our previous experiments on isolated rat pancreas gave evidence for a P2 purinergic receptor on the insulin-secreting B cell. This work was designed to investigate whether the stimulation of insulin release by phosphorylated adenosine derivatives could also be observed in rat isolated Langerhans islets and whether this stimulation was accompanied by changes in calcium uptake. The results indicate that two structural methylene analogues of ATP and ADP (alpha,beta-methylene ATP and alpha,beta-methylene ADP) display an insulin stimulatory effect comparable to that of ATP, confirming the membrane action of the latter. It was also found that calcium uptake increased concomitantly with insulin release under the effect of alpha,beta-methylene ADP; on the other hand this agent also increased the total exchangeable calcium content of islets at isotopic equilibrium. Verapamil, a blocker of voltage-sensitive calcium channels, counteracted the stimulation of insulin release and also blocked the increase in total exchangeable calcium content. These results demonstrate the involvement of calcium in the stimulus-secretion coupling of insulin release induced by an activator of P2 purinergic receptors and suggest the implication of voltage-sensitive calcium channels.