Facilitation of Quantal Release Induced by a D1-like Receptor on Bovine Chromaffin Cells

Abstract

Dopaminergic receptors are found on bovine adrenal chromaffin cells and have been implicated in the facilitation of an inward calcium current [Artalejo et al., (1990) Nature 348, 239-242] that could enhance release. However, previous studies using incubations of long duration (minutes) with dopaminergic receptor antagonists have found instead an inhibition of catecholamine release. In this work we used brief (subsecond) chemical depolarizing stimuli to reexamine the role of dopaminergic receptors on exocytosis from bovine adrenal chromaffin cells. Responses to consecutive depolarizing stimuli were compared using amperometry to monitor vesicular release events and intracellular fura-2 to examine Ca2+ dynamics within individual cells. Restoration of intracellular Ca2+ levels to their initial values following exposure to 60 mM K+ was found to be prolonged unless the exposure was brief (0.5 s) and the cells were maintained at 37 degrees C. However, with these optimum conditions, a second stimulation evoked more exocytotic events than the first. This effect was blocked by SCH-23390, a D1 antagonist, in a dose dependent fashion, but not by raclopride, a D2 antagonist. The D1 agonist, SKF-38393, enhanced the number of exocytotic events as did prior exposure of the cell to epinephrine. Taken together, the data indicate that released catecholamines can enhance their own release by interaction with a D1-like receptor on bovine adrenal chromaffin cells.