Opioids suppress basal and nicotine-induced catecholamine secretion via a stabilizing effect on actin filaments

Catecholamine secretion and actin filament disassembly are closely coupled in chromaffin cells. Opioid suppression of catecholamine secretion is fast and transient, both characteristics of actin filament involvement. The aim of the present work was to test the hypothesis that opioids suppress catech olamine secretion via an inhibitory effect on actin filament disassembly. F or this purpose we used the PC12 rat pheochromocytoma cell Line. Norepineph rine and dopamine were measured by enzyme-linked immunosorbent assay or RIA . Polymerized actin was measured by rhodamine-phalloidin and visualized by confocal laser scanning microscopy. Opioids suppressed basal catecholamine secretion. The onset of this effect was fast and transient, peaking at 2 mi n, and was reversible by opioid antagonists. Synchronously, opioids suppres sed actin filament disassembly; this was also reversible by opioid antagoni sts. Cytochalasin B prevented the inhibitory effect of opioids on catechola mine secretion, in addition, opioids suppressed the stimulatory effect of n icotine on catecholamine secretion and actin depolymerization. Changes in a ctin cytoskeleton in neuron-like PC12 cells make them resistant to both eff ects of opioids, i.e. on catecholamine secretion and actin disassembly. in conclusion, our data suggest that the suppressive effect of opioids on basa l and nicotine-induced catecholamine secretion may result from an opioid-pr ovoked stabilization of cortical actin. It also appears that basal catechol amine secretion is associated with opioid-sensitive machinery regulating th e continuous formation of short-lived areas of cortical actin filament disa ssembly.