D2-Like Receptors Mediate Dopamine-Inhibited Insulin Secretion via Ion Channels in Rat Pancreatic β-Cells

Dopamine (DA) has a vital role in the central nervous system and also modulates lipid and glucose metabolism. The present study aimed to investigate the effect of dopamine on insulin secretion and the underlying mechanisms in rat pancreatic β-cells. Data from the radioimmunoassay indicated that dopamine inhibited insulin secretion in a glucose- and dose-dependent manner. This inhibitory effect of dopamine was mediated mainly by D2-like receptors, but not D1-like receptors. Whole-cell patch-clamp recordings showed that dopamine decreased voltage-dependent Ca(2+) channel currents, which could be reversed by inhibition of the D2-like receptor. Dopamine increased voltage-dependent potassium (K(V)) channel currents and shortened action potential duration, which was antagonized by inhibition of D2-like receptors. Further experiments showed that D2-like receptor activation by quinpirole increased K(V) channel currents. In addition, using calcium imaging techniques, we found that dopamine reduced intracellular Ca(2+) concentration, which was also reversed by D2-like receptor antagonists. Similarly, quinpirole was found to decrease intracellular Ca(2+) levels. Taken together, these findings demonstrate that dopamine inhibits insulin secretion mainly by acting on D2-like receptors, inhibiting Ca(2+) channels, and activating Kv channels. This process results in shortened action potential duration and decreased intracellular Ca(2+) levels in β-cells. This work offers new insights into a glucose-dependent mechanism whereby dopamine regulates insulin secretion.