Opiate, cannabinoid, and eicosanoid signaling converges on common intracellular pathways nitric oxide coupling

Fimiani, Caterina; Liberty, Thomas; Aquirre, Andrew J; Amin, Irum; Ali, Nafees F; Stefano, George B.

doi:10.1016/s0090-6980(98)00068-9

Cited by 49 publications

(32 citation statements)

References 76 publications

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“…In fact, the intracellular signals set in motion by 2AG and CP55,940 entail the production of NO and PGE 2 involving the induction of iNOS and COX-2, the increase in the intracellular levels of cGMP, and the blunting of the antigen-induced increase in intracellular calcium. The link between endocannabinoids and the NO pathway is well established by experiments showing that AEA stimulates the generation of NO in a host of experimental conditions, both in vivo and in vitro (Stefano et al, 1996(Stefano et al, , 1997Prevot et al, 1998;Fimiani et al, 1999a). The present experiments add further evidence to the relationship between the endocannabinoids and the NO system by showing that 2AG and CP55,940 generate NO from guinea pig mast cells.…”

Section: Discussionsupporting

confidence: 74%

The Endocannabinoid 2-Arachidonylglycerol Decreases the Immunological Activation of Guinea Pig Mast Cells: Involvement of Nitric Oxide and Eicosanoids

Vannacci¹,

Giannini²,

Passani³

et al. 2004

J Pharmacol Exp Ther

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The antigen-induced release of histamine from sensitized guinea pig mast cells was dose-dependently reduced by endogenous (2-arachidonylglycerol; 2AG) and exogenous [(1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol (CP55,940)] cannabinoids. The inhibitory action afforded by 2AG and CP55,940 was reversed by N- [(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide (SR144528), a selective cannabinoid 2 (CB 2 ) receptor antagonist, and left unchanged by the selective CB 1 antagonistThe inhibitory action of 2AG and CP55,940 was reduced by the unselective nitric-oxide synthase (NOS) inhibitor N-monomethyl-L-arginine methylester (L-NAME) and reinstated by L-arginine, the physiological substrate. The inhibitory action of 2AG and CP55,940 was also reduced by the unselective cyclooxygenase (COX) inhibitor indomethacin and the selective COX-2 blocker rofecoxib. Both 2AG and CP55,940 significantly increased the production of nitrite from mast cells, which was abrogated by benzyl)acetamidine (1400W), a selective inducible NOS (iNOS) inhibitor. Nitrite production consistently paralleled a CP55,940-induced increase in the expression of iNOS protein in mast cells. Both 2AG and CP55,940 increased the generation of prostaglandin E 2 from mast cells, which was abrogated by indomethacin and rofecoxib and parallel to the CP55,940-induced expression of COX-2 protein.Mast cell challenge with antigen was accompanied by a net increase in intracellular calcium levels. Both cannabinoid receptor ligands decreased the intracellular calcium levels, which were reversed by SR144528 and L-NAME. In unstimulated mast cells, both ligands increased cGMP levels. The increase was abrogated by SR144528, L-NAME, indomethacin, and rofecoxib. Our results suggest that 2AG and CP55,940 decreased mast cell activation in a manner that is susceptible to a CB 2 receptor antagonist and to inhibition of nitric oxide and prostanoid pathways.The immunosuppressive effect of tetrahydrocannabinol (THC) was formerly reported both in humans (Nahas et al., 1974) and experimental animals (Coffey et al., 1996). More recently, the effects of THC on human immune functions and host defense have been reviewed, providing evidence that THC can suppress the human immune response in a host of leukocyte subsets and alveolar macrophages, further stressing the relationship between marijuana smoking and immunologically-related diseases (Klein et al., 1998).Of the immunocompetent cells, mast cells are strategically placed in tissues that interface with the external environment and vary in the way in which their activation is modified by endocannabinoids. In the rat ear pin, the degranulation of resident mast cells induced by substance P is fully abrogated by the endogenous ligands at cannabinoid (CB) receptors arachidonylethanolamide (anandamide; AEA) and palmitoylethanol-

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Section: Discussionsupporting

confidence: 74%

The Endocannabinoid 2-Arachidonylglycerol Decreases the Immunological Activation of Guinea Pig Mast Cells: Involvement of Nitric Oxide and Eicosanoids

Vannacci¹,

Giannini²,

Passani³

et al. 2004

J Pharmacol Exp Ther

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“…Atherosclerosis, a chronic inflammatory disease, is the primary cause of myocardial infarction and stroke. Administration of THC reduces development of experimental atherosclerosis and its cardiac and cerebral manifestations (10). However, a protective role for CB1 blockade was also observed, reinforcing the complexity of cannabinoid biology.…”

Section: Phytocannabinoids: Tetrahydrocannabinol and Cannabidiolmentioning

confidence: 91%

Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation

Burstein

Zurier

2009

AAPS J

123

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Abstract. This review covers reports published in the last 5 years on the anti-inflammatory activities of all classes of cannabinoids, including phytocannabinoids such as tetrahydrocannabinol and cannabidiol, synthetic analogs such as ajulemic acid and nabilone, the endogenous cannabinoids anandamide and related compounds, namely, the elmiric acids, and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. A possible mechanism for these actions is suggested involving increased production of eicosanoids that promote the resolution of inflammation. This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process.

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“…Morphine, given its long latency before increases in its levels are detected, arises after trauma/inflammation to down regulate these processes in neural and immune tissues [7,35,36]. Anandamide, by being part of the always present arachidonate and eicosanoid signaling processes serve to maintain tonal NO in vascular tissues [37]. We surmise that estrogen, since testosterone or progesterone don"t exert this NO generating action, provides an extra-degree of immunocyte and vascular down regulation in females.…”

Section: Amentioning

confidence: 93%

Estrogen and Morphine Modulate Their Own and the Other's Human Endothelial Receptor Expression via Nitric Oxide

Cadet¹,

Prévot²,

Beauvillain³

et al. 2009

Am. J. Biomed. Sci.

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In previous studies we have demonstrated that  3 and estrogen  receptor subtypes are present in human vascular endothelial cells and coupled to constitutive nitric oxide synthase (cNOS) stimulation. In the present report we demonstrate that internal thoracic artery (ITA) endothelia express a  opioid receptor mRNA transcript and exposure of these transcripts to increasing concentrations of 17 -estradiol significantly diminishes ITA  opioid receptor expression. Exposure of ITA endothelia to SNAP, a NO donor, also diminishes  opioid receptor gene expression, suggesting that NO mediates, in an L-NAME (N G -nitro-L-arginine methyl ester) and tamoxifen sensitive manner, 17 -estradiol"s down regulating action. ITA endothelia also express an estrogen  receptor subtype and, when treated with morphine, in an L-NAME and naloxone sensitive manner diminishes the  estrogen receptor"s expression. This demonstrates an interactive receptor mediated process via NO for both signaling agents. Additionally, morphine and estrogen actions were examined for their ability to alter adhesion to ITA segments. This treatment resulted in a concentration dependent decrease in monocyte adherence to the vessels at 30 min. Exposure to both agents did not decrease monocyte adherence further. Exposure to L-NAME or either naloxone or tamoxifen, opiate and estrogen cell surface receptor inhibitors, respectively, blocked the decrease in monocyte adherence, demonstrating NO involvement and a specific receptor mediated process. In conclusion, this study demonstrates that an interactive receptor mediated process via NO for both signaling agents is present.

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Opiate, cannabinoid, and eicosanoid signaling converges on common intracellular pathways nitric oxide coupling

Cited by 49 publications

References 76 publications

The Endocannabinoid 2-Arachidonylglycerol Decreases the Immunological Activation of Guinea Pig Mast Cells: Involvement of Nitric Oxide and Eicosanoids

The Endocannabinoid 2-Arachidonylglycerol Decreases the Immunological Activation of Guinea Pig Mast Cells: Involvement of Nitric Oxide and Eicosanoids

Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation

Estrogen and Morphine Modulate Their Own and the Other's Human Endothelial Receptor Expression via Nitric Oxide

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