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Morphine-induced conformational changes in human monocytes, granulocytes, and endothelial cells and in invertebrate
H I Magazine1, Y Liu, T V Bilfinger
1Department of Biology, Queens College and the Graduate School of the City University of New York, NY 11367, USA.
Abstract:
We evaluated the contribution of nitric oxide (NO) to morphine-induced rounding of spontaneously activated (mobile) ameboid human monocytes, granulocytes, or arterial endothelial cells and invertebrate immunocytes and microglia. Morphine induced significant rounding and inactivation of ameboid cells within 20 min except for arterial endothelial cells, which became rounded 24 h after morphine exposure. The effects of morphine on cell conformation were blocked in the presence of N-nitro-L-arginine, a nitric oxide synthase inhibitor. Treatment of cells with the NO donor, sodium nitroprusside, induced cell rounding similar to that observed following morphine exposure, suggesting that NO release may mediate morphine-induced changes in cell conformation. The contribution of NO release to morphine-induced cell rounding was determined by direct evaluation of NO concentration in real-time using a NO-specific amperometric probe. Significant increases in NO concentration were observed 2 min after morphine stimulation, whereas morphine-induced NO release was markedly impaired by pretreatment with N-nitro-L-arginine or the opiate alkaloid antagonist, naloxone. In contrast, opioid peptides failed to induce NO release, consistent with our previous observations that demonstrated the failure of opioid peptides to promote cell rounding. Taken together, these data suggest that morphine-induced NO release may be mediated by activation of the opiate alkaloid-selective, opioid peptide-insensitive micro3 receptor, and that functional coupling of morphine to NO production has been conserved during evolution and may modulate cellular activation.
Insights
Morphine causes cell rounding by releasing nitric oxide (NO), a process blocked by antagonists and mediated by specific opioid receptors. This NO pathway is conserved across species, influencing cellular activation.
Area of Science:
- Immunology
- Cell Biology
- Neuroscience
Background:
- Morphine, an opiate alkaloid, affects various cell types.
- Nitric oxide (NO) is a signaling molecule involved in cellular processes.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in morphine-induced cell rounding.
- To identify the receptors and pathways involved in morphine's effects on cell conformation.
Main Methods:
- Exposure of human and invertebrate cells to morphine and NO donors.
- Inhibition of nitric oxide synthase (NOS) with N-nitro-L-arginine.
- Measurement of NO concentration using amperometric probes.
- Use of naloxone to block opiate alkaloid receptors.
Main Results:
- Morphine induced cell rounding and inactivation in various ameboid cells, except arterial endothelial cells.
- N-nitro-L-arginine blocked morphine-induced cell rounding, while a NO donor mimicked the effect.
- Morphine significantly increased NO levels, which was inhibited by N-nitro-L-arginine and naloxone.
- Opioid peptides did not induce NO release or cell rounding.
Conclusions:
- Nitric oxide (NO) mediates morphine-induced cell rounding and inactivation.
- The micro3 receptor, selective for opiate alkaloids, appears to mediate NO release.
- The functional coupling of morphine to NO production is evolutionarily conserved and may regulate cellular activation.