caa a22 4500 469121181 CHVBK 20180323133139.0 cr unu---uuuuu 170328e19920301xx s 000 0 eng 10.1007/BF02245427 doi (NATIONALLICENCE)springer-10.1007/BF02245427 Endopeptidase 24.15 inhibition and opioid antinociception [Elektronische Daten] [Benjamin Kest, Marion Orlowski, Richard Bodnar] Whereas endopeptidase 24.11 cleaves the Gly-Phe bond in both Met- and Leu-enkephalin, endopeptidase 24.15 rapidly converts dynorphin A1-8, alpha and beta-neoendorphin into Leu-enkephalin, and Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) into Met-enkephalin. Inhibitors of both endopeptidase 24.11 and endopeptidase 24.15 each produce antinociception, and inhibitors of endopeptidase 24.11 increase the magnitude of enkephalin antinociception. The present study compared the central antinociceptive effect of an inhibitor of endopeptidase 24.15, N-[1-(R-S)-carboxy-3-phenyl-propyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) with one of endopeptidase 24.11 N-[1-(RS)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (cFP-F-pAB) upon central opioid antinociception induced by MERGL, met-enkephalin and dynorphin A1-8. cFP-AAF-pAB, but not cFP-F-pAB increased MERGL antinociception on the tail-flick and jump tests. In contrast, cFP-F-pAB, but not cFP-AAF-pAB increased met-enkephalin antinociception. Whereas central dynorphin A1-8 failed to induce antinociception itself, co-administration of cFP-AAF-pAB and dynorphin A1-8 increased nociceptive thresholds. This effect was not accompanied by motor dysfunction, but was blocked by systemic pretreatment with naloxone or central pretreatment with naltrexone or nor-binaltorphamine, but not beta-funaltrexamine. These data indicate that endopeptidase 24.15 may be responsible for the degradation of specific opioid peptides (e.g., MERGL, dynorphin), and that this process may prevent the full expression of their antinociceptive properties. Springer-Verlag, 1992 Endopeptidase 24.15 nationallicence Endopeptidase 24.11 nationallicence MERGL nationallicence Dynorphin nationallicence A1-8 nationallicence Nor-binaltorphamine nationallicence Antinociception nationallicence Kest Benjamin Department of Psychology, Neuropsychology Doctoral Sub-Program, Queens College, CUNY, 65-30 Kissena Boulevard, 11367, Flushing, NY, USA aut Orlowski Marion Department of Pharmacology, Mount Sinai School of Medicine, 10029, New York, NY, USA aut Bodnar Richard Department of Psychology, Neuropsychology Doctoral Sub-Program, Queens College, CUNY, 65-30 Kissena Boulevard, 11367, Flushing, NY, USA aut Psychopharmacology Springer-Verlag 106/3(1992-03-01), 408-416 0033-3158 106:3<408 1992 106 213 https://doi.org/10.1007/BF02245427 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245427 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kest Benjamin Department of Psychology, Neuropsychology Doctoral Sub-Program, Queens College, CUNY, 65-30 Kissena Boulevard, 11367, Flushing, NY, USA aut NATIONALLICENCE 700 1- Orlowski Marion Department of Pharmacology, Mount Sinai School of Medicine, 10029, New York, NY, USA aut NATIONALLICENCE 700 1- Bodnar Richard Department of Psychology, Neuropsychology Doctoral Sub-Program, Queens College, CUNY, 65-30 Kissena Boulevard, 11367, Flushing, NY, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 106/3(1992-03-01), 408-416 0033-3158 106:3<408 1992 106 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer