Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many neuropeptides involved in pain perception are generated by endoproteolytic cleavages of their precursor proteins by the proprotein convertases PC1 and PC2. To investigate the role of PC2 in nociception and analgesia, we tested wild-type and PC2-null mice for their responses to mechanical and thermal nociceptive stimuli, before and after a short swim in cold or warm water. Basal responses and responses after a cold swim were similar between the two groups. However, after a short forced swim in warm water, PC2-null mice were significantly less responsive to the stimuli than wild-type mice, an indication of increased opioid-mediated stress-induced analgesia. The enhanced analgesia in PC2-null mice may be caused by an accumulation of opioid precursor processing intermediates with potent analgesic effects, or by loss of anti-opioid peptides.
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PMID:Increased stress-induced analgesia in mice lacking the proneuropeptide convertase PC2. 1690 51

Dynorphin opioid neuropeptides mediate neurotransmission for analgesia and behavioral functions. Dynorphin A, dynorphin B, and alpha-neoendorphin are generated from prodynorphin by proteolytic processing. This study demonstrates the significant role of the cysteine protease cathepsin L for producing dynorphins. Cathepsin L knockout mouse brains showed extensive decreases in dynorphin A, dynorphin B, and alpha-neoendorphin that were reduced by 75%, 83%, and 90%, respectively, compared to controls. Moreover, cathepsin L in brain cortical neurons was colocalized with dynorphins in secretory vesicles, the primary site of neuropeptide production. Cellular coexpression of cathepsin L with prodynorphin in PC12 cells resulted in increased production of dynorphins A and B. Comparative studies of PC1/3 and PC2 convertases showed that PC1/3 knockout mouse brains had a modest decrease in dynorphin A, and PC2 knockout mice showed a minor decrease in alpha-neoendorphin. Overall, these results demonstrate a prominent role for cathepsin L, jointly with PC1/3 and PC2, for production of dynorphins in brain.
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PMID:Cathepsin L participates in dynorphin production in brain cortex, illustrated by protease gene knockout and expression. 1983 64