Document Detail


The gastric effects of UFP-112, a new nociceptin/orphanin receptor agonist, in physiological and pathological conditions.
MedLine Citation:
PMID:  17765363     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nociceptin/orphanin FQ (N/OFQ), the endogenous NOP receptor ligand, centrally modulates gastric motor and secretory functions and prevents ethanol-induced gastric lesions in rats. A recently synthesized N/OFQ analog, [(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112), acts as a highly potent and selective peptide agonist for NOP receptors and produces longer-lasting in vitro and in vivo effects in mice than the natural ligand N/OFQ. In this study, we evaluated the effects of centrally (intracerebroventricularly/icv) and peripherally (intraperitoneally/ip) injected UFP-112 on gastric emptying and gastric acid secretion, and on the development of gastric mucosal lesions induced by 50% ethanol in the rat. When injected icv, it dose-dependently delayed gastric emptying of a phenol red meal (by up to 70%), decreased gastric secretion in water-loaded rats after 90 pylorus ligature, and reduced ethanol-induced gastric lesions (by up to 87%). In all three assays, UFP-112 was more effective than N/OFQ. The highly selective NOP receptor antagonist, UFP-101, decreased the efficacy of UFP-112, thus confirming that central NOP receptors mediate inhibitory control on these functional and pathological conditions in rats. Ip injected N/OFQ and UFP-112 induced non-dose-related gastric hypersecretory and antiulcer effects, which UFP-101 partially abolished. Ip N/OFQ appeared equiactive but about 30-100 times less potent than ip UFP-112 in stimulating gastric acid secretion and preventing lesion formation. When ip injected, both UFP-112 and N/OFQ left gastric emptying in rats unchanged, suggesting that peripheral NOP receptors have a role in mediating gastric hypersecretory and antiulcer effects but are not involved in regulating gastric motility. In addition, the inhibitory effects induced by this novel NOP receptor agonist lasted longer than those induced by N/OFQ. In conclusion, UFP-112 is a promising new pharmacological tool for studying the functional roles of the central and peripheral N/OFQ receptor system.
Authors:
M Broccardo; R Guerrini; G Morini; C Polidori; S Agostini; C Petrella; G Improta
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-27
Journal Detail:
Title:  Peptides     Volume:  28     ISSN:  0196-9781     ISO Abbreviation:  Peptides     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-24     Completed Date:  2008-01-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008690     Medline TA:  Peptides     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1974-81     Citation Subset:  IM    
Affiliation:
Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gastric Emptying / drug effects
Opioid Peptides / pharmacology*
Rats
Receptors, Opioid / agonists*
Stomach / drug effects*
Chemical
Reg. No./Substance:
0/Opioid Peptides; 0/Receptors, Opioid; 0/nociceptin receptor; 0/nociceptin-amide, Nphe(1)-(pF)Phe(4)-Aib(7)-Arg(14)-Lys(15)-

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