Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

• MeSH
• antiflogistika imunologie   metabolismus   MeSH
• cholinergní látky imunologie   metabolismus   MeSH
• lidé MeSH
• nervus vagus imunologie   metabolismus   MeSH
• neuroimunomodulace fyziologie   MeSH
• neurony cholinergní imunologie   metabolismus   MeSH
• signální transdukce fyziologie   MeSH
• zánět imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Trimedoxime is a bisquaternary oxime that is widely used in the treatment of organophosphorous poisoning caused by tabun and paraoxon. We tested its affinity to acetylcholinesterase (AChE), its mechanism of interaction and effect on the cholinergic system of the rat bladder. The half maximal inhibitory concentration (IC50) of trimedoxime to recombinant AChE was found to be 82.0 mM ± 30.1 mM. This represents a weak inhibition. Its interaction with AChE seems to be very similar to obidoxime - one aromatic nucleus interacts with the peripheral anionic site and the other with the residues TYR337 and TYR341 inside the cavity. Also the oxime moiety is moving towards the catalytic triade ready for the reactivation of the inhibited AChE. In the organ bath experiment no significant effect of trimedoxime was observed on the contraction of the detrusor caused by the muscarinic agonist metacholine.

• Klíčová slova
• acetylcholinesterase, trimedoxime, antidote, muscaricnic receptors, reactivation,
• MeSH
• acetylcholinesterasa farmakokinetika   farmakologie   účinky léků   MeSH
• antidota farmakologie   terapeutické užití   MeSH
• cholinergní antagonisté farmakokinetika   farmakologie   terapeutické užití   MeSH
• cholinergní látky farmakologie   imunologie   izolace a purifikace   MeSH
• experimenty na zvířatech MeSH
• financování organizované MeSH
• močový měchýř MeSH
• organofosforové sloučeniny farmakokinetika   farmakologie   toxicita   MeSH
• pesticidy farmakokinetika   farmakologie   toxicita   MeSH
• potkani Sprague-Dawley MeSH
• reaktivátory cholinesterázy farmakokinetika   farmakologie   terapeutické užití   MeSH
• receptory muskarinové účinky léků   MeSH
• synergismus léků MeSH
• trimedoxim farmakokinetika   farmakologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH