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 microns), intermediate (16-25 microns), or large ( > 25 microns) neurons. Substance P-like immunoreactivity was detected mainly in the small and intermediate neurons. The delta, kappa, and mu opioid receptor agonists [D-Ser2,Leu5]enkephalin-Thr (DSLET), U69593, and [D-Ala2, MePhe4, Glyol5]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 microM 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 microM). Inhibition of the K(+)-stimulated increase by 1 microM DSLET or U69593 was greater in small and intermediate neurons than in large neurons.
Tang
T
T
Department of Pharmacology, Uniformed Services University of Health Sciences, Bethesda, MD 20814-4799, USA.
Stevens
B A
BA
Cox
B M
BM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D013373:Substance P / Q000032:analysis
D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D013373:Substance P; D004743:Enkephalin, Leucine; D011189:Potassium Chloride; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; C045444:U 69593; D002118:Calcium