Effects of pimozide and apomorphine on insulin secretion from the perfused rat pancreas

The effects of apomorphine, a partial agonist of dopamine, and of pimozide, an agent commonly used as an antagonist of dopamine, on insulin secretion from the perfused rat pancreas were studied. Apomorphine (10 and 100 microM) significantly reduced the insulin released in response to a stimulating glucose load. As judged from the perfusion pressure vasoconstriction could not account for the inhibitory action. The effect of apomorphine was not reversed by phentolamine infused to block alpha-receptors. Pimozide (1 microM) slightly weakened the inhibitory effect of apomorphine (10 microM) but failed to completely restore a normal secretion. An increase of the pimozide concentration (10 microM) revealed, however, that the agent itself reduced the glucose-induced insulin release. Thus a differentiation of dopamine agonistic and antagonistic effects could not be achieved with the aid of pimozide.