EVIDENCE FOR 2 DIFFERENT TYPES OF P2 RECEPTORS STIMULATING INSULIN-SECRETION FROM PANCREATIC B-CELL

1 Adenine nucleotides have been shown to stimulate insulin secretion b y acting on P2 receptors of the P2Y type. Since there have been some d iscrepancies in the insulin response of different analogues of ATP and ADP, we investigated whether two different types of P2 receptors exis t on pancreatic B cells. The effects of alpha,beta-methylene ATP, whic h is more specific for the P2X subtype, were studied in vitro in pancr eatic islets and isolated perfused pancreas from rats, in comparison w ith the potent P2Y receptor agonist ADP beta S. 2 In isolated islets, incubated with a slightly stimulating glucose concentration (8.3 mM), alpha,beta-me ATP (200 mu M) and ADP beta S (50 mu M) similarly stimul ated insulin secretion; by contrast, under a non stimulating glucose c oncentration (8.3 mM), alpha,beta-me ATP was still effective whereas A DP beta S was not. In the same way, in islets perifused with 3 mM gluc ose, alpha,beta-me ATP but not ADP beta S induced a partial but signif icant reduction in the peak Rb-86 efflux induced by the ATP-dependent potassium channel opener diazoxide. 3 In the isolated pancreas, perfus ed with a non stimulating glucose concentration (4.2 mM), ADP beta S a nd alpha,beta-me ATP (5-50 mu M), administered for 10 min, induced an immediate, transient and concentration-dependent increase in the insul in secretion; their relative potency was not significantly different. In contrast, with a slightly stimulating glucose concentration (8.3 mM ), ADP beta S was previously shown to be 100 fold more potent than alp ha,beta-me ATP. Furthermore, at 4.2 mM glucose a second administration of alpha,beta-me ATP was ineffective. In the same way, ADP beta S was also able to desensitize its own insulin response. At 3 mM glucose, a lpha,beta-me ATP as well as ADP beta S (50 mu M) induced a transient s timulation of insulin secretion and down regulated the action of each other. 4 These results give evidence that pancreatic B cells, in addit ion to P2Y receptors, which potentiate glucose-induced insulin secreti on, are provided with P2X receptors, which transiently stimulate insul in release at low non-stimulating glucose concentration and slightly a ffect the potassium conductance of the membrane.