External ATP mimics carbachol in initiating calcium mobilization from pancreatic beta-cells conditioned by previous exposure to glucose.

1 Exposure to ATP (2-200 microM) resulted in a prominent peak of 45Ca efflux, when beta-cell-rich pancreatic islets from ob/ob-mice were perifused with a Ca2+-deficient medium. ADP and the stable alpha/beta-methylene analogues of ATP and ADP also had stimulatory effects. 2 The nucleotide initiation of 45Ca efflux mimicked that obtained with carbachol both in requiring previous exposure to glucose and in being more pronounced after replacing extracellular Na+ by K+. 3 It was possible to induce repeated peaks of stimulated 45Ca efflux, when the exposure to ATP was interrupted with intervals of perifusion with glucose-containing media. 4 The observations are consistent with the existence of P2-purinoceptors in islets, suggesting that these receptors mediate a similar mobilization of calcium as noted when activating polyphosphoinositide breakdown with carbachol. In view of the high contents of ATP and ADP in the beta-cell secretory granules, activation of P2-purinoceptors should be considered as a possible mechanism for amplification of the initial insulin secretory response.