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Effects Of Doxycycline On Mice Neuromuscular Junction, In Situ

Author(s):

Natália Tribuiani, Jocimar de Souza, Marcos Antônio de Queiroz Junior, Denicezar Angelo Baldo, Valéria de Campos Orsi and Yoko Oshima-Franco*  

Abstract:


Background: The antibacterial mechanism of doxycycline is known, but on the nerve-muscle apparatus is yet unclear.

Objective: To combine molecular targets of the neuromuscular machinery using the neuronal blocker effect doxycycline, a semisynthetic second-generation tetracycline derivative, on mice neuromuscular preparations, in situ.

Methods: Doxycycline was assessed at the neurotransmission; presynaptic; synaptic cleft; and postsynaptic, including the muscle fiber, using the traditional myographic technique. Preliminarily, doxycycline showed an "all or nothing" effect, being "all" obtained with 4 µM and "nothing", with 1-3 µM. The rationale of this study was to apply known pharmacological tools against the blocker effect of 4 µM doxycycline such as F55-6 (Casearia sylvestris), CaCl2 (or Ca2+), atropine, neostigmine, polyethylene glycol (PEG 400), and d-Tubocurarine. The evaluation of cholinesterase enzyme activity, the diaphragm muscle histology, and protocols on the neuromuscular preparation submitted to indirect or direct stimuli were complementary.

Results: Doxycycline does not affect cholinesterase activity nor cause damage to skeletal muscle diaphragm; acts on ryanodine receptor, sarcolemmal membrane, and on neuronal sodium channel with a postjunctional consequence due to the decreased availability of muscle nicotinic acetylcholine receptors.

Conclusions: In conclusion, using the blocker effect we showed that doxycycline acts on multiple targets, among them, is antagonized by F55-6, a neuronal Na+-channel agonist and Ca2+, but not by neostigmine.

Keywords:

Antibiotics, Doxycycline, Molecular targets, Neuromuscular Junction, Tetracycline, Phrenic-nerve diaphragm preparation

Affiliation:

Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO), Rodovia Raposo Tavares, km 92.5, 18023-000, Sorocaba, SP, Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO), Rodovia Raposo Tavares, km 92.5, 18023-000, Sorocaba, SP, Biomedicine Course, University of Sorocaba (UNISO), Rodovia Raposo Tavares, km 92.5, 18023-000, Sorocaba, SP, Laboratory of Applied Nuclear Physics, University of Sorocaba (UNISO), Rodovia Raposo Tavares, km 92.5, 18023-000, Sorocaba, SP, Support Laboratory 2. University of Sorocaba (UNISO), Rodovia Raposo Tavares, km 92.5, 18023-000, Sorocaba, SP, Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO), Rodovia Raposo Tavares, km 92.5, 18023-000, Sorocaba, SP



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