Short- and long-term influences of calcitonin gene-related peptide on the synthesis of acetylcholinesterase in mammalian myotubes

Short- and long-term influences of calcitonin gene-related peptide on the synthesis of acetylcholinesterase in mammalian myotubes

Autor Costa Junior, Valter Luiz da Google Scholar
Lapa, Antonio José Autor UNIFESP Google Scholar
Godinho, Rosely Oliveira Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo 1 the present study analyses the short- (15 min-2 h) and long-term (24-48 h) influences of calcitonin gene-related peptide (CGRP) on acetylcholinesterase (AChE) expression in the rat cultured skeletal muscle and the signal transduction events underlying CGRP actions.2 To assess the effect of CGRP on AChE synthesis, myotubes were pre-exposed to the irreversible AChE inhibitor diisopropyl fluorophosphate (DFP) and treated with CGRP or forskolin, an adenylyl cyclase (AC) activator. Treatment of myotubes with 1 - 100 nM CGRP for 2 h increased by up to 42% the synthesis of catalytically active AChE with a parallel increase in the intracellular cyclic AMP.3 the stimulation of AChE synthesis induced by CGRP was mimicked by direct activation of AC with 3 - 30 muM forskolin. in contrast, pre-treatment of cultures with 100 nM CGRP for 20 h reduced by 37% the subsequent synthesis of AChE, resulting in a 15% decrease in total AChE activity after 48 h CGRP treatment.4 Moreover, 24 h treatment of myotubes with 100 nM CGRP reduced by 54% the accumulation of cyclic AMP induced by a subsequent CGRP treatment.5 These findings indicate that, in skeletal muscle cells, CGRP modulates the AChE expression in a time-dependent manner, initially stimulating the enzyme synthesis through a cyclic AMP-dependent mechanism. the decreased AChE synthesis observed after long-term CGRP treatment suggests that CGRP signalling system is subject to desensitization or down-regulation, that might function as an important adaptative mechanism of the muscle fibre in response to long-term changes in neuromuscular transmission.
Palavra-chave calcitonin gene-related peptide
adenylyl cyclase
neuromuscular junction
skeletal muscle
Idioma Inglês
Data de publicação 2001-05-01
Publicado em British Journal of Pharmacology. Basingstoke: Nature Publishing Group, v. 133, n. 2, p. 229-236, 2001.
ISSN 0007-1188 (Sherpa/Romeo, fator de impacto)
Publicador Nature Publishing Group
Extensão 229-236
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000168750800002
Endereço permanente

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