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Doctoral Thesis
DOI
10.11606/T.42.2008.tde-10092008-133641
Document
Author
Full name
Lidiana Duarte de Almeida Paula
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Markus, Regina Pekelmann (President)
Avellar, Maria Christina Werneck de
Oliveira, Antonio Carlos
Sannomiya, Paulina
Visconti, Maria Aparecida
Title in Portuguese
Influência da melatonina e análogos sobre a expressão de colinoceptores nicotínicos em miotubos de rato em cultura.
Keywords in Portuguese
a-Bungarotoxina
AMP cíclico
Calmodulina
Colinoceptores nicotínicos
Cultura de miotubos
Melatonina
Abstract in Portuguese
O objetivo deste estudo foi caracterizar a influência da melatonina sobre a atividade de colinoceptores nicotínicos em miotubos de rato em cultura e determinar seu mecanismo de ação. Neste modelo verificamos que a melatonina reduz a densidade de sítios de ligação para ?-bungarotoxina e também a produção de AMP cíclico induzida por forscolina, adenosina e CGRP, mas não por isoprenalina. Estes efeitos foram mimetizados por N-acetilserotonina e 4-P-PDOT, mas não por 2-Iodo-melatonina e 5-MCA-NAT, e foram bloqueados por luzindol. A redução da produção de AMP cíclico não foi inibida por toxina pertussis. O calmidazolium bloqueia tanto a redução da densidade dos colinoceptores nicotínicos quanto a inibição da produção de AMP cíclico. Avaliando a via da guanilil ciclase determinamos que melatonina e calmidazolium inibem a produção de GMP cíclico induzida por KCl. Podemos concluir que a melatonina não está atuando via receptores de membrana, mas provavelmente, está atuando internamente bloqueando a enzima calmodulina.
Title in English
Influence of melatonin and analogues on the nicotinic-colinoceptors expression in myotube culture from rats.
Keywords in English
a-Bungarotoxin
Calmodulin
Cyclic AMP
Melatonin
Myotube culture
Nicotinic colinoceptors
Abstract in English
The objective of this study was characterize the influence of melatonin on the nicotinic-colinoceptors activity in myotube culture from rats and seeks its action mechanism. In this model we demonstrated that melatonin decreases the binding-sites density to ?-bungarotoxin and cyclic AMP synthesis induced by forskolin, adenosine and CGRP, but not by isoprenaline. These effects were mimetized by N-acetylserotonin and 4-P-PDOT, but not by 2-iodomelatonin and 5-MCA-NAT and were blocked by luzindol. Reduction of the cyclic AMP synthesis was not inhibited by pertussis toxin. Calmidazolium blocked both the reduction of nicotinic colinoceptors density and the inhibition of AMP cyclic synthesis. After evaluate the guanylyl cyclase via, we determined that melatonin and calmidazolium inhibit the cyclic GMP synthesis induced by KCl. Then we concluded that melatonin does not act via membrane receptors, but probably, acts blocking the calmodulin enzyme.
 
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Publishing Date
2008-09-22
 
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