| The novel endomorphin degradation blockers Tyr-Pro-DClPhe-Phe-NH (EMDB-1) and Tyr-Pro-Ala-NH (EMDB-2) prolong endomorphin-2 action in rat ileum in vitro. | |
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MedLine Citation:
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PMID: 20456368 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The endogenous opioid system is involved in the control of gastrointestinal (GI) motility. The potential use of endogenous MOR ligands, endomorphins (EMs), as therapeutics is limited because of their rapid enzymatic degradation and short duration of action. Targeting enzymatic degradation is an approach to prolong EM activity. In the present study, we characterized the effects of novel blockers of EM degradation in GI tissue preparation in vitro. The effects of actinonin, diprotin A (DIP) and the novel peptide EM degradation blockers Tyr-Pro-DClPhe-Phe-NH(2) (EMDB-1), Tyr-Pro-Ala-NH(2) (EMDB-2) and Tyr-Pro-Ala-OH (EMDB-3) on EM-2-mediated inhibition of electrically induced cholinergic twitch contractions were compared in rat ileum in vitro using an organ bath. EMDB-1 and EMDB-2 significantly prolonged the inhibitory effect of EM-2 on smooth muscle contractility in rat ileum. EMDB-2 extended the EM-2 action for up to 60 min compared to 10 min in controls and was more potent than the conventional peptidase inhibitor DIP. EMDB-1 and EMDB-2 are potent EM degradation blockers, which prolong the inhibitory effects of EM-2 on smooth muscle contractility in rat ileum. These novel compounds may be of future use when targeting the endogenous opioid system in the treatment of GI motility disorders such as diarrhea. |
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Authors:
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Jakub Fichna; Renata Perlikowska; Katarzyna Gach; Jean-Claude do-Rego; Aurore Cravezic; Anna Janecka; Martin A Storr |
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Publication Detail:
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Type: Letter; Research Support, Non-U.S. Gov't Date: 2010-04-23 |
Journal Detail:
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Title: Chemical biology & drug design Volume: 76 ISSN: 1747-0285 ISO Abbreviation: Chem Biol Drug Des Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-10-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101262549 Medline TA: Chem Biol Drug Des Country: England |
Other Details:
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Languages: eng Pagination: 77-81 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Hydroxamic Acids / chemistry, pharmacology Ileum / drug effects*, metabolism Oligopeptides / chemistry, metabolism, pharmacology* Rats |
| Chemical | |
Reg. No./Substance:
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0/Hydroxamic Acids; 0/Oligopeptides; 0/endomorphin 2; 13434-13-4/actinonin; 90614-48-5/diprotin A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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