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• W1971516646 endingPage "1543" @default.
• W1971516646 startingPage "1536" @default.
• W1971516646 abstract "Abstract l ‐Kyotorphin ( l ‐KTP), an endogenous analgesic neuropeptide, is a substrate for aminopeptidases and a proton‐coupled oligopeptide transporter, PEPT2. This study examined the CSF efflux, antinociceptive response, and hydrolysis kinetics in brain of l ‐KTP and its synthetic diastereomer d ‐kyotorphin ( d ‐KTP) in wild‐type and Pept2 null mice. CSF clearance of l ‐KTP was slower in Pept2 null mice than in wild‐type animals, and this difference was reflected in greater l ‐KTP‐induced analgesia in Pept2 null mice. Moreover, dose‐response analyses showed that the ED50 of l ‐KTP in Pept2 ‐deficient animals was one‐fifth of the value observed in Pept2 ‐competent animals (4 vs. 21 nmol for null vs. wild‐type mice, respectively). In contrast, the ED50 of d ‐KTP was very similar between the two genotypes (9–10 nmol). Likewise, there was little difference between genotypes in slope factor or baseline effects of l ‐KTP and d ‐KTP. The enhanced antinociceptive response to l ‐KTP in Pept2 null mice could not be explained by differences in neuropeptide degradation as Vmax and Km values did not differ between genotypes. Our results demonstrate that PEPT2 can significantly impact the analgesic response to an endogenous neuropeptide by altering CSF (and presumably brain interstitial fluid) concentrations and that it may influence the disposition and response to exogenous peptide/mimetic substrates." @default.
• W1971516646 created "2016-06-24" @default.
• W1971516646 creator A5022534249 @default.
• W1971516646 creator A5024720824 @default.
• W1971516646 creator A5066304805 @default.
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• W1971516646 date "2009-05-12" @default.
• W1971516646 modified "2023-10-16" @default.
• W1971516646 title "Enhanced antinociceptive response to intracerebroventricular kyotorphin in <i>Pept2</i> null mice" @default.
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• W1971516646 doi "https://doi.org/10.1111/j.1471-4159.2009.06090.x" @default.
• W1971516646 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2898572" @default.
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• W1971516646 hasPublicationYear "2009" @default.
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