Opioid regulation of intracellular free calcium in cultured mouse dorsal root ganglion neurons

Opioid agonists induced an increase in the intracellular free calcium concentration ([Ca2+](i)) or an inhibition of K+ (25 mM)-stimulated increase in [Ca2+](i) in different subsets of mouse dorsal root ganglion (DRG) neurons, The total neuronal population was grouped into three classes according to somatic diameter and defined as small (<16 mu m), intermediate (16-25 mu m), or large (>25 mu m) neurons. Substance P-like immunoreactivity was detected mainly in the small and intermediate neurons, The delta, kappa, and mu opioid receptor agonists [D-Ser(2), Leu(5)]enkekphalin-Thr (DSLET), U69593, and [D-Ala(2), MePhe(4), Glyol(5)]enkephalin (DAMGO) each induced a transient increase in [Ca2+](i) in a small fraction (<30%) of neurons, The increases in [Ca2+](i) were blocked by the opioid antagonist naloxone, The dihydropyridine-sensitive calcium channel blocker nifedipine also blocked the increase in [Ca2+](i) induced by 1 mu M DSLET. The rank order of potency (percentage of cells responding to each opioid agonist) was DSLET > U69593 > DAMGO, The opioid-induced increase in [Ca2+](i) was observed mainly in large neurons, with a low incidence in small and intermediate neurons, Opioid agonists also caused inhibition of K+-stimulated increases in [Ca2+](i), which were blocked by naloxone (1 mu M). Inhibition of the K+-stimulated increase by 1 mu M DSLET or U69593 was greater in small and intermediate neurons than in large neurons. (C) 1996 Wiley-Liss, Inc.