Morphine stimulates nitric oxide release from invertebrate microglia.
Morphine stimulates nitric oxide (NO) release in human endothelial cells. To determine whether this mechanism also occurs in invertebrates, the mussel Mytilus edulis was studied. Exposure of excised ganglia to morphine for 24 h resulted in a significant dose-dependent decrease in microglial egress that was naloxone sensitive. In coincubating the excised ganglia with morphine and the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), an increase in microglial egress was observed, suggesting that morphine may stimulate microglia to release NO. Morphine exposure to these cells in vitro resulted in NO release (39.4 +/- 4.9 nM), a phenomenon found to be naloxone sensitive (10(-6) M; NO level = 5.9 +/- 2.6 nM) and L-NAME sensitive (10(-4) M; NO level = 2.8 +/- 1.8 nM). Opioid peptides did not stimulate NO release, indicating that the process was mediated by the opiate alkaloid selective mu 3 receptor. Coincubation of microglia with L-arginine or the superoxide scavenger, superoxide dismutase, resulted in significantly higher NO levels observed following morphine stimulation. Taken together, the data demonstrate that morphine can stimulate NO release in cells obtained from an invertebrate that represents an animal 500 million years divergent in evolution from man, underscoring the significance of this process and further substantiating the critical importance of morphine as a naturally occurring signal molecule.
Liu
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Y
Neuroscience Research Institute, State University of New York at Old Westbury 11568, USA.
Shenouda
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D
Bilfinger
T V
TV
Stefano
M L
ML
Magazine
H I
HI
Stefano
G B
GB
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D049872:Bivalvia; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D018847:Opioid Peptides / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018847:Opioid Peptides; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester