Antinociceptive effect of [Met5]enkephalin semicarbazide is not affected by dipeptidyl carboxypeptidase-I
Article first published online: 14 NOV 2011
Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 18, Issue 2, pages 92–96, February 2012
How to Cite
Rezaee, Z., Arabanian, S. A., Balalaie, S., Ahmadiani, A., Khalaj, L. and Nasoohi, S. (2012), Antinociceptive effect of [Met5]enkephalin semicarbazide is not affected by dipeptidyl carboxypeptidase-I. J. Peptide Sci., 18: 92–96. doi: 10.1002/psc.1420
- Issue published online: 27 JAN 2012
- Article first published online: 14 NOV 2011
- Manuscript Accepted: 24 AUG 2011
- Manuscript Revised: 17 AUG 2011
- Manuscript Received: 12 MAY 2011
- enkephalin amide;
- tail-flick latency response;
- dipeptidyl carboxypeptidase-I
Dipeptidyl carboxypeptidase-I is an enzyme involved in the biological degradation of enkephalins. It has been suggested that C-terminal amidation of enkephalins enhances their resistance to dipeptidyl carboxypeptidase-I-mediated biodegradation. In this study, a novel [Met5]enkephalin amide (MEA) analogue [Met5]enkephalin (ME)-semicarbazide synthesized by another laboratory in our group was assessed for its antinociceptive effects compared with ME-ethylamide, MEA and ME, using tail flick test. To protect the administered drugs from biodegradation, rats were pretreated with peptidase inhibitors including amastatin, phosphoramidon and captopril. Then captopril (dipeptidyl carboxypeptidase-I inhibitor) was deleted from the peptidase inhibitors' combination for evaluating in vivo resistance of the synthetic drugs to dipeptidyl carboxypeptidase-I.
According to the results, ME-semicarbazide and MEA were resistant enough to dipeptidyl carboxypeptidase-I to exert their strong antinociception following intrathecal administration even in the absence of captopril, whereas the antinociceptive effects produced by ME-ethylamide (10 nmol) were abolished in rats not pretreated with captopril, indicating that significant amounts of the ME-ethylamide were degraded by dipeptidyl carboxypeptidase-I. Replacement of the amide moiety of MEA with semicarbazide provides a new ME derivative, with high analgesic effects as well as more resistance to dipeptidyl carboxypeptidase-I-mediated biodegradation. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.