Serotonin 5‐HT2A Receptor Activation Inhibits Cytokine‐stimulated Inducible Nitric Oxide Synthase in C6 Glioma Cells a

  title={Serotonin 5‐HT2A Receptor Activation Inhibits Cytokine‐stimulated Inducible Nitric Oxide Synthase in C6 Glioma Cells a},
  author={Keith J. Miller and Hugo Gonz{\'a}lez},
  journal={Annals of the New York Academy of Sciences},
ABSTRACT: C6‐glioma cells endogenously express both 5‐HT2A receptors and inducible nitric oxide synthase (iNOS). iNOS can be induced by transcriptional activation to produce nitric oxide (NO) in response to a challenge with the pro‐inflammatory cytokines TNF‐α and IFN‐γ. Experiments were conducted to determine whether 5‐HT2A receptor activation could modify the production of NO in response to the inducing agents. 1 μM DOI produced a dose‐dependent inhibition of the cytokine‐inducted nitrite… 
Angiotensin II‐Induced Decrease in Expression of Inducible Nitric Oxide Synthase in Rat Astroglial Cultures
Data indicate a role for PKC in the inhibitory actions of Ang II on iNOS expression in cultured astroglia and the reduction of lipopolysaccharide‐induced nitrite accumulation by Ang II was attenuated by the selective PKC inhibitor chelerythrine.
Serotonin 5-Hydroxytryptamine2A Receptor Activation Suppresses Tumor Necrosis Factor-α-Induced Inflammation with Extraordinary Potency
The results indicate that activation of 5-HT2A receptors represents a novel, and extraordinarily potent, potential therapeutic avenue for the treatment of disorders involving TNF-α-mediated inflammation.
Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: involvement of 5-hydroxytryptamine2A receptors.
The findings suggest that the inhibition of TNF-alpha production by 5- HT involves the participation of the 5-HT(2A) receptor subtypes in PBMC, and support a role of 5-ht in inflammation through its effect on cytokine production inPBMC.
  • K. M. Rao
  • Biology
    Journal of toxicology and environmental health. Part B, Critical reviews
  • 2000
A comprehensive table of cell types that produce NO together with the effects of agents used to study iNOS regulation, as a ready reference for the investigators in the field, and to summarize recent observations dealing with iNos signal transduction mechanisms are presented.
Nitric oxide and glioma: a target for novel therapy?
The biological role of nitric oxide in the central nervous system and gliomas and its current and future possibilities in neuro-oncology are discussed.
A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice
Data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS.
Functions of serotonin in hypoxic pulmonary vascular remodeling
The contribution of serotonin, its receptors and transporter in lung hypoxic responses is discussed and why expression of pulmonary vascular remodeling factors is not modified in hypoxic 5-HT2B receptor mutant mice is explained.


Nitric Oxide Synthase Expression in Glial Cells: Suppression by Tyrosine Kinase Inhibitors
Results indicate that induction of astroglial iNOS expression requires tyrosine kinase activity, and the presence of genistein prevented both lipopolysaccharide‐ and cytokine‐induced NOS activity in a dose‐dependent manner.
Attenuation of inducible nitric oxide synthase gene expression by delta 9-tetrahydrocannabinol is mediated through the inhibition of nuclear factor- kappa B/Rel activation.
This series of experiments indicates that NF-kappa B/Rel is positively regulated by the cAMP cascade to help initiate iNOS gene expression in response to LPS stimulation of macrophages, which is attenuated by delta 9-THC through the inhibition of cAMP signaling.
Angiotensin II inhibits cytokine-stimulated inducible nitric oxide synthase expression in vascular smooth muscle cells.
The results indicate that Ang II negatively modulates cytokine-induced NO production by blocking iNOS expression via the AT1 receptor in VSMC and suggest that protein kinase C could be involved in this process.
Serotonin 5‐HT2C Receptor Stimulates Cyclic GMP Formation in Choroid Plexus
It is demonstrated that receptor activation also triggers the formation of cyclic GMP (cGMP), and in addition to triggering phosphoinositide turnover, choroid plexus serotonin 5‐HT2C receptors trigger cGMP formation in a calcium‐sensitive manner.
Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide.
Delineation of these two cooperative regions explains at the level of transcription how IFN-gamma and LPS act in concert to induce maximally the mac-NOS gene and, furthermore, howIFN-Gamma augments the inflammatory response to LPS.
A new interpretation of the involvement of serotonin in delayed-type hypersensitivity. Serotonin-2 receptor antagonists inhibit contact sensitivity by an effect on T cells.
It is suggested that late-acting DTH effector T cells might express functional 5-HT2R, and that these receptors might require in vivo activation in order for the T cells to locally produce the inflammatory lymphokine-dependent aspects of DTH.