Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Botulinum toxin is used to induce transient graded paresis by chemodenervation in the treatment of focal hyperkinetic movement disorders. While the molecular events occurring in motoneurons after mechanical nerve lesioning leading to muscle paresis are well known, they have been investigated to a lesser extent after chemodenervation. We therefore examined the expression of enkephalin (ENK), acidic fibroblast growth factor (aFGF), neurotensin (NT), galanin (GAL), substance P (SP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in rat spinal motoneurons after chemodenervation of the gastrocnemius. In order to precisely localize the motoneurons targeting the injection site, retrograde tracing was performed in additional rats by using Fluorogold injections. ENK expression was upregulated in the region corresponding to the Fluorogold positive motoneurons, but also on the contralateral side and in more distant parts of the spinal cord. The highest upregulation occurred 7 to 14 days after injections and decreased over a period of three months. At 8 days, aFGF was slightly downregulated in all regions studied, single motoneurons showed NT expression, while expression of GAL, SP, VIP, and NPY could be detected neither in controls nor in toxin-treated animals. These alterations in gene expression were strikingly different from those described after axotomy. Our present findings give additional demonstration of the considerable plasticity of the adult spinal cord after botulinum toxin treatment.
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PMID:Enkephalin and aFGF are differentially regulated in rat spinal motoneurons after chemodenervation with botulinum toxin. 1068 1

Botulinum toxin (BT) has been perceived as a lethal threat for many centuries. In the early 1980s, this perception completely changed when BT's therapeutic potential suddenly became apparent. We wish to give an overview over BT's mechanisms of action relevant for understanding its therapeutic use. BT's molecular mode of action includes extracellular binding to glycoprotein structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated by blockade of substance P, glutamate and calcitonin gene-related peptide.
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PMID:Botulinum toxin: mechanisms of action. 1565 Mar 6

This review describes therapeutically relevant mechanisms of action of botulinum toxin (BT). BT's molecular mode of action includes extracellular binding to glycoproteine structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain-barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated through blockade of substance P, glutamate and calcitonin gene related peptide.
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PMID:Botulinum toxin: mechanisms of action. 1583 90