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Melatonin modulates nitric oxide production in cerebellum cells culture

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Author(s):
Daiane Gil Franco
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
Defense date:
Examining board members:
Regina Pekelmann Markus; Cristoforo Scavone; Cláudia Lúcia Martins da Silva
Advisor: Regina Pekelmann Markus
Abstract

Melatonin, a serotonin derivative, is the main product of the pineal gland. Can also be produced by various extra¬pineal sites as retina, gastrointestinal tract, immune cells, among others. In mammals it has different roles, and, classically, is known to act as a chemistry mediator of the darkness. The rhythmic release of this hormone into the blood and cerebrospinal fluid marks the light¬dark cycle and the seasons to the internal organs. Moreover, melatonin acts as a modulator of the immune system and inflammation, a cytoprotective agent and reduces free radicals formation. The mechanisms of action are also diverse and vary from membrane receptors to intracellular interactions. Here we show that melatonin inhibits the production of NO activated by ACh or BK in cultured cerebellar granule cells. These agonists activate constitutive NOS, which are dependent on increased intracellular Ca2+. Melatonin also blocks acetylcholine-induced Ca2+ intracellular increase, suggesting that, this indolamine effects on NO production activated by ACh is, probably, an effect on the increase of intracellular Ca2+. Lipopolysaccharide of gram¬negative bacteria wall activates the transcription of inducible NOS isoform. Melatonin inhibits the enzyme expression and NO production in granule cerebellar cells activated with the bacterial endotoxin. Our data shows that these effects are dependent on inhibition of nuclear factor kappa B pathway. In summary, the present work shows that melatonin inhibits constitutive NOS activity and inducible NOS expression. These effects are dependent on specific mechanisms and should be related to different cellular functions. (AU)

FAPESP's process: 07/06423-0 - Effect of melatonin on the reactivity of nicotinic acetylcholinergic receptors and the activity of constitutive and inducible nitric oxide synthase in cerebellar granule cells.
Grantee:Daiane Gil Franco
Support Opportunities: Scholarships in Brazil - Master