Nonopioid receptor-mediated effects of U-50,488H on [Ca2+]i and extracellular dopamine in PC12 cells

The present studies were carried out to determine the effects of a kappa-opioid receptor agonist on cytosolic Ca(2+) concentration, [Ca(2+)](i), and extracellular dopamine in undifferentiated PC12 cells. The kappa-opioid receptor agonist U-50,488H caused concentration-dependent increases in [Ca(2+)](i) and extracellular dopamine. Neither effect was blocked by the selective kappa-opioid receptor antagonist nor-binaltorphimine. Increases in extracellular dopamine content and [Ca(2+)](i) caused by U-50,488H were correlated positively in the presence of extracellular Ca(2+); however, reduction of extracellular Ca(2+) abolished the increase in [Ca(2+)](i), but not that in dopamine. The latter observation suggests that stimulation of exocytotic release is not the primary mechanism involved in the increase in extracellular dopamine caused by U-50,488H. Effects on dopamine synthesis or catabolism also seem unlikely because the enhancement of extracellular dopamine occurred rapidly, and the amount of a major metabolite of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), was not affected. In any event, neither the increase in [Ca(2+)](i) nor the increase in extracellular dopamine caused by U-50,488H is mediated by the kappa-opioid receptor.