The Journal of Immunology, Vol 156, Issue 12 4845-4850, Copyright © 1996 by American Association of Immunologists

ARTICLES

Morphine-induced conformational changes in human monocytes, granulocytes, and endothelial cells and in invertebrate immunocytes and microglia are mediated by nitric oxide

HI Magazine, Y Liu, TV Bilfinger, GL Fricchione and GB Stefano
Department of Biology, Queens College and the Graduate School of the City University of New York, NY 11367, USA.

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.

This article has been cited by other articles:

				P. Cadet, K. J. Mantione, W. Zhu, R. M. Kream, M. Sheehan, and G. B. Stefano A Functionally Coupled {micro}3-Like Opiate Receptor/Nitric Oxide Regulatory Pathway in Human Multi-Lineage Progenitor Cells J. Immunol., November 1, 2007; 179(9): 5839 - 5844. [Abstract] [Full Text] [PDF]

				W. Zhu, P. Cadet, G. Baggerman, K. J. Mantione, and G. B. Stefano Human White Blood Cells Synthesize Morphine: CYP2D6 Modulation J. Immunol., December 1, 2005; 175(11): 7357 - 7362. [Abstract] [Full Text] [PDF]

				H.-E. Wu, J. Thompson, H.-S. Sun, M. Terashvili, and L. F. Tseng Antianalgesia: Stereoselective Action of dextro-Morphine over levo-Morphine on Glia in the Mouse Spinal Cord J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1101 - 1108. [Abstract] [Full Text] [PDF]

				I. Tegeder and G. Geisslinger Opioids As Modulators of Cell Death and Survival--Unraveling Mechanisms and Revealing New Indications Pharmacol. Rev., September 1, 2004; 56(3): 351 - 369. [Abstract] [Full Text] [PDF]

				P. Cadet, K. J. Mantione, and G. B. Stefano Molecular Identification and Functional Expression of {micro}3, a Novel Alternatively Spliced Variant of the Human {micro} Opiate Receptor Gene J. Immunol., May 15, 2003; 170(10): 5118 - 5123. [Abstract] [Full Text] [PDF]

				G. B. Stefano, P. Cadet, K. Mantione, J. J. Cho, D. Jones, and W. Zhu Estrogen Signaling at the Cell Surface Coupled to Nitric Oxide Release in Mytilus edulis Nervous System Endocrinology, April 1, 2003; 144(4): 1234 - 1240. [Abstract] [Full Text] [PDF]

				S. W. Park, J. Li, H. H. Loh, and L.-N. Wei A Novel Signaling Pathway of Nitric Oxide on Transcriptional Regulation of Mouse kappa Opioid Receptor Gene J. Neurosci., September 15, 2002; 22(18): 7941 - 7947. [Abstract] [Full Text] [PDF]

				H. I. Magazine, J. Chang, Y. Goumon, and G. B. Stefano Rebound from Nitric Oxide Inhibition Triggers Enhanced Monocyte Activation and Chemotaxis J. Immunol., July 1, 2000; 165(1): 102 - 107. [Abstract] [Full Text] [PDF]

				Y. Goumon, F. Casares, S. Pryor, L. Ferguson, B. Brownawell, P. Cadet, C. M. Rialas, I. D. M. Welters, D. Sonetti, and G. B. Stefano Ascaris suum, an Intestinal Parasite, Produces Morphine J. Immunol., July 1, 2000; 165(1): 339 - 343. [Abstract] [Full Text] [PDF]

				G. B. Stefano, P. Cadet, C. Breton, Y. Goumon, V. Prevot, J. P. Dessaint, J.-C. Beauvillain, A. S. Roumier, I. Welters, and M. Salzet Estradiol-stimulated nitric oxide release in human granulocytes is dependent on intracellular calcium transients: evidence of a cell surface estrogen receptor Blood, June 15, 2000; 95(12): 3951 - 3958. [Abstract] [Full Text] [PDF]

				A. Chen, S. M. Kumar, C. L. Sahley, and K. J. Muller Nitric Oxide Influences Injury-Induced Microglial Migration and Accumulation in the Leech CNS J. Neurosci., February 1, 2000; 20(3): 1036 - 1043. [Abstract] [Full Text] [PDF]

				S. Fukuda, T. Yasu, D. N. Predescu, and G. W. Schmid-Schonbein Mechanisms for Regulation of Fluid Shear Stress Response in Circulating Leukocytes Circ. Res., January 7, 2000; 86 (1): e13 - e18. [Abstract] [Full Text] [PDF]

				G. B. Stefano, V. Prevot, J.-C. Beauvillain, C. Fimiani, I. Welters, P. Cadet, C. Breton, J. Pestel, M. Salzet, and T. V. Bilfinger Estradiol Coupling to Human Monocyte Nitric Oxide Release Is Dependent on Intracellular Calcium Transients: Evidence for an Estrogen Surface Receptor J. Immunol., October 1, 1999; 163(7): 3758 - 3763. [Abstract] [Full Text] [PDF]

				K. D. Srivastava and H. I. Magazine Thrombin Receptor Activation Inhibits Monocyte Spreading by Induction of ETB Receptor-Coupled Nitric Oxide Release J. Immunol., November 1, 1998; 161(9): 5039 - 5044. [Abstract] [Full Text] [PDF]

				F. T. KANEKO, A. C. ARROLIGA, R. A. DWEIK, S. A. COMHAIR, D. LASKOWSKI, R. OPPEDISANO, M. J. THOMASSEN, and S. C. ERZURUM Biochemical Reaction Products of Nitric Oxide as Quantitative Markers of Primary Pulmonary Hypertension Am. J. Respir. Crit. Care Med., September 1, 1998; 158(3): 917 - 923. [Abstract] [Full Text] [PDF]

				M.C. Grimm, A. Ben-Baruch, D.D. Taub, O.M.Z. Howard, J.H. Resau, J.M. Wang, H. Ali, R. Richardson, R. Snyderman, and J.J. Oppenheim Opiates Transdeactivate Chemokine Receptors: delta  and µ Opiate Receptor-mediated Heterologous Desensitization J. Exp. Med., July 20, 1998; 188(2): 317 - 325. [Abstract] [Full Text] [PDF]

				M. Salzet, V. Chopin, J.-l. Baert, I. Matias, and J. Malecha Theromin, a Novel Leech Thrombin Inhibitor J. Biol. Chem., September 29, 2000; 275(40): 30774 - 30780. [Abstract] [Full Text] [PDF]