Haloperidol, a dopaminergic antagonist: somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas.
The effect of haloperidol, a dopaminergic antagonist, on insulin and glucagon secretion was investigated using the isolated, perfused canine pancreas. Haloperidol at 4 X 10(-7) to 10(-5) mol/l caused a dose-dependent inhibition of glucagon release both at low (25 mg/100 ml) and high glucose concentrations (150 mg/100 ml). At the low glucose concentration insulin release was already maximally suppressed. At the high glucose concentration haloperidol (4 X 10(-7) to 10(-5) mol/1) also caused a dose-dependent inhibition of insulin release. Haloperidol (10(-5) mol/1) inhibited dramatically pancreatic A and B cell responses to isoproterenol (2 ng/ml), acetylcholine (1 mumol/1) and arginine (5 mmol/1). The inhibitory effect of haloperidol on both glucagon and insulin release could be eliminated by increasing perfusate calcium concentration from 1.3 to 8.8 mmol/1. These findings suggested that haloperidol blocks glucagon and insulin release in a somatostatin-like manner by affecting a fundamental step of the stimulus-secretion coupling, probably by interfering with calcium handling of the pancreatic A and B cells.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D013004:Somatostatin
D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D001120:Arginine; D005947:Glucose; D006220:Haloperidol; D000109:Acetylcholine; D002118:Calcium