Differential effects of purinergic and cholinergic activation on the hydrolysis of membrane polyphosphoinositides in rat pancreatic islets.

This work was designed to investigate the effects of a P2 purinoreceptor agonist, alpha, beta-methylene ADP, on membrane polyphosphoinositide hydrolysis in relation to insulin release from rat isolated islets of Langerhans. The effects of this stable structural analogue of ADP (10(-4) M) were compared with those of a muscarinic cholinergic agonist, carbachol (10(-4) M). The interaction between alpha, beta-methylene ADP and carbachol was studied on polyphosphoinositide breakdown and insulin secretion. The experiments were performed in presence of a slightly stimulating glucose concentration (8.3 mM). Whereas carbachol-induced insulin release was accompanied by a concomitant increase in inositol phosphates accumulation, alpha, beta-methylene ADP at the same concentration produced a similar insulin secretion without eliciting an accumulation of inositol phosphates. The combined effect of both substances added simultaneously resulted in a significant increase in insulin release as compared with the secretion induced by either substance used separately. By contrast, the accumulation of inositol phosphates induced by both substances was not different from the accumulation induced by carbachol alone. These results seem to rule out the involvement of polyphosphoinositide hydrolysis in the coupling mechanism between P2 purinoreceptor activation and insulin response of the B cell. Moreover, purinergic stimulation appears not to interact with the effect of muscarinic stimulation on polyphosphoinositide breakdown.