Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas

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Abstract
The effect of haloperidol, a dopaminergic antagonist, on insulin and glucagon secretion was investigated using the isolated, perfused canine pancreas. Haloperidol at 4 × 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 × 10−7 to 10−5 mol/l) also caused a dose-dependent inhibition of insulin release. Haloperidol (10−5 mol/l) inhibited dramatically pancreatic A and B cell responses to isoproterenol (2 ng/ml), acetylcholine (1 μmol/l) and arginine (5mmol/l). 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/l. 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.