IN-VIVO AND IN-VITRO EFFECTS OF ADENOSINE-5'-O-12-THIODIPHOSPHATE) ONPANCREATIC HORMONES IN DOGS

Adenosine-5'-0-(2-thiodiphosphate) (ADP beta S), a P-2y purinergic ago nist, has been shown to be a potent insulin secretagogue on the isolat ed rat pancreas. In the present work the effects of ADP beta S on insu lin, somatostatin, and glucagon secretions were investigated in dogs. In vivo, in anesthetized fasted dogs, i.v. ADP beta S (0.1 mg kg(-1)) induced an immediate increase in insulin and somatostatin-like immunor eactivity (SLI) but not in glucagon pancreaticoduodenal outputs. In co nscious fasted dogs, i.v. ADP beta S (0.1 mg kg(-1)) produced an immed iate and transient augmentation in plasma insulin levels but not in pl asma SLI and glucagon levels. In vitro, the effects of ADP beta S were investigated on the isolated uncinate process of dog pancreas, from n ormal and alloxan-diabetic animals. In normal uncinate process, in pre sence of 8.3 mill glucose, ADP beta S (1 mu M) stimulated insulin and SLI releases but not glucagon release. On uncinate process from diabet ic animals, ADP beta S (1 mu M) retained its stimulating effects but t he responses were impaired as compared with normal dogs: Insulin respo nse was drastically diminished and SLI response strongly enhanced. In conclusion, ADP beta S is a potent insulin secretory agent in dog. Thi s P-2y purinoceptor agonist, which exerts a direct stimulatory effect on pancreatic SLI, is interestingly devoid of direct glucagonotropic p roperties.