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Cannabinoid regulation of nitric oxide synthase I (nNOS) in neuronal cells.
J Neuroimmune Pharmacol. 2009 Sep; 4(3):338-49.JN

Abstract

In our previous studies, CB(1) cannabinoid receptor agonists stimulated production of cyclic GMP and translocation of nitric oxide (NO)-sensitive guanylyl cyclase in neuronal cells (Jones et al., Neuropharmacology 54:23-30, 2008). The purpose of these studies was to elucidate the signal transduction of cannabinoid-mediated neuronal nitric oxide synthase (nNOS) activation in neuronal cells. Cannabinoid agonists CP55940 (2-[(1S,2R,5S)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), WIN55212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate), and the metabolically stable analog of anandamide, (R)-(+)-methanandamide stimulated NO production in N18TG2 cells over a 20-min period. Rimonabant (N-(piperidin-lyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-H-pyrazole-3-carboxamide), a CB(1) receptor antagonist, partially or completely curtailed cannabinoid-mediated NO production. Inhibition of NOS activity (N (G)-nitro-L: -arginine) or signaling via Gi/o protein (pertussis toxin) significantly limited NO production by cannabinoid agonists. Ca(2+) mobilization was not detected in N18TG2 cells after cannabinoid treatment using Fluo-4 AM fluorescence. Cannabinoid-mediated NO production was attributed to nNOS activation since endothelial NOS and inducible NOS protein and mRNA were not detected in N18TG2 cells. Bands of 160 and 155 kDa were detected on Western blot analysis of cytosolic and membrane fractions of N18TG2 cells, using a nNOS antibody. Chronic treatment of N18TG2 cells with cannabinoid agonists downregulated nNOS protein and mRNA as detected using Western blot analysis and real-time polymerase chain reaction, respectively. Cannabinoid agonists stimulated NO production via signaling through CB(1) receptors, leading to activation of Gi/o protein and enhanced nNOS activity. The findings of these studies provide information related to cannabinoid-mediated NO signal transduction in neuronal cells, which has important implications in the ongoing elucidation of the endocannabinoid system in the nervous system.

Authors+Show Affiliations

Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19365734

Citation

Carney, Skyla T., et al. "Cannabinoid Regulation of Nitric Oxide Synthase I (nNOS) in Neuronal Cells." Journal of Neuroimmune Pharmacology : the Official Journal of the Society On NeuroImmune Pharmacology, vol. 4, no. 3, 2009, pp. 338-49.
Carney ST, Lloyd ML, MacKinnon SE, et al. Cannabinoid regulation of nitric oxide synthase I (nNOS) in neuronal cells. J Neuroimmune Pharmacol. 2009;4(3):338-49.
Carney, S. T., Lloyd, M. L., MacKinnon, S. E., Newton, D. C., Jones, J. D., Howlett, A. C., & Norford, D. C. (2009). Cannabinoid regulation of nitric oxide synthase I (nNOS) in neuronal cells. Journal of Neuroimmune Pharmacology : the Official Journal of the Society On NeuroImmune Pharmacology, 4(3), 338-49. https://doi.org/10.1007/s11481-009-9153-7
Carney ST, et al. Cannabinoid Regulation of Nitric Oxide Synthase I (nNOS) in Neuronal Cells. J Neuroimmune Pharmacol. 2009;4(3):338-49. PubMed PMID: 19365734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid regulation of nitric oxide synthase I (nNOS) in neuronal cells. AU - Carney,Skyla T, AU - Lloyd,Michael L, AU - MacKinnon,Shanta E, AU - Newton,Doshandra C, AU - Jones,Jenelle D, AU - Howlett,Allyn C, AU - Norford,Derek C, Y1 - 2009/04/14/ PY - 2008/07/02/received PY - 2009/03/18/accepted PY - 2009/4/15/entrez PY - 2009/4/15/pubmed PY - 2009/10/14/medline SP - 338 EP - 49 JF - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JO - J Neuroimmune Pharmacol VL - 4 IS - 3 N2 - In our previous studies, CB(1) cannabinoid receptor agonists stimulated production of cyclic GMP and translocation of nitric oxide (NO)-sensitive guanylyl cyclase in neuronal cells (Jones et al., Neuropharmacology 54:23-30, 2008). The purpose of these studies was to elucidate the signal transduction of cannabinoid-mediated neuronal nitric oxide synthase (nNOS) activation in neuronal cells. Cannabinoid agonists CP55940 (2-[(1S,2R,5S)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), WIN55212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate), and the metabolically stable analog of anandamide, (R)-(+)-methanandamide stimulated NO production in N18TG2 cells over a 20-min period. Rimonabant (N-(piperidin-lyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-H-pyrazole-3-carboxamide), a CB(1) receptor antagonist, partially or completely curtailed cannabinoid-mediated NO production. Inhibition of NOS activity (N (G)-nitro-L: -arginine) or signaling via Gi/o protein (pertussis toxin) significantly limited NO production by cannabinoid agonists. Ca(2+) mobilization was not detected in N18TG2 cells after cannabinoid treatment using Fluo-4 AM fluorescence. Cannabinoid-mediated NO production was attributed to nNOS activation since endothelial NOS and inducible NOS protein and mRNA were not detected in N18TG2 cells. Bands of 160 and 155 kDa were detected on Western blot analysis of cytosolic and membrane fractions of N18TG2 cells, using a nNOS antibody. Chronic treatment of N18TG2 cells with cannabinoid agonists downregulated nNOS protein and mRNA as detected using Western blot analysis and real-time polymerase chain reaction, respectively. Cannabinoid agonists stimulated NO production via signaling through CB(1) receptors, leading to activation of Gi/o protein and enhanced nNOS activity. The findings of these studies provide information related to cannabinoid-mediated NO signal transduction in neuronal cells, which has important implications in the ongoing elucidation of the endocannabinoid system in the nervous system. SN - 1557-1904 UR - https://www.unboundmedicine.com/medline/citation/19365734/Cannabinoid_regulation_of_nitric_oxide_synthase_I__nNOS__in_neuronal_cells_ L2 - https://doi.org/10.1007/s11481-009-9153-7 DB - PRIME DP - Unbound Medicine ER -