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Pharm Res
1997 Jun 01;146:713-9. doi: 10.1023/a:1012185919153.
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Dynorphin peptides: antagonists of melanocortin receptors.
Quillan JM, Sadée W.
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PURPOSE: To identify possible targets that mediate the non-opioid effects of dynorphin-A (DynA), effects that include inflammation and aggravation of traumatic nerve injury.
METHOD: We examined dynorphin peptides for functional interaction with the closely related melanocortin (MC) system.
RESULTS: DynA-(1-13)NH2 and other related opioid dynorphin peptides antagonize the human MC1, MC3 and MC4 receptors, and an amphibian MC receptor, with dissociation constants (Kd's) of 40 to 150 nM. The affinity of dynorphin's interaction with MC receptors is therefore greater than with other previously proposed non-opioid targets of dynorphin, which require micromolar concentrations. Dynorphin also antagonizes the adrenocorticotropic hormone (ACTH; MC2) receptor and an MC-like receptor endogenous to COS-7 cells, but with lower efficacy. In contrast DynA had no effect on seven control receptors and was only weakly effective at two others. Metabolites of dynorphin derived from cleavage of the amino terminal Tyr residue, such as DynA(2-17), lack opioid activity yet still produce a number of well established non-opioid effects. These des-Tyr derivatives also antagonized each of the five MC receptors examined.
CONCLUSIONS: DynA peptides were found to antagonize MC receptors in vitro with potencies that parallel those reported for pharmacological non-opioid effects of dynorphins in vivo. The combination of DynA and its active metabolites may reach levels sufficient to inhibit MC receptors physiologically. Dynorphin inhibition of MC receptors could prove to be an example of crosstalk between two distinct yet phylogenetically related neurotransmitter systems.
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9210186 ???displayArticle.link???Pharm Res ???displayArticle.grants???[+]
Akil,
Endogenous opioids: biology and function.
1984, Pubmed
Akil,
Endogenous opioids: biology and function.
1984,
Pubmed Alvaro,
Morphine down-regulates melanocortin-4 receptor expression in brain regions that mediate opiate addiction.
1996,
Pubmed Bertolini,
Alpha-MSH and other ACTH fragments improve cardiovascular function and survival in experimental hemorrhagic shock.
1986,
Pubmed Bertolini,
Adrenocorticotropin reversal of experimental hemorrhagic shock is antagonized by morphine.
1986,
Pubmed Chavkin,
Dynorphin is a specific endogenous ligand of the kappa opioid receptor.
1982,
Pubmed Chen,
The mechanism of action for the block of NMDA receptor channels by the opioid peptide dynorphin.
1995,
Pubmed Contreras,
Antagonism of morphine-induced analgesia, tolerance and dependence by alpha-melanocyte-stimulating hormone.
1984,
Pubmed Daniolos,
Action of light on frog pigment cells in culture.
1990,
Pubmed
,
Xenbase Datta,
Attenuation of morphine analgesia by alpha-MSH, MIF-I, melatonin and naloxone in the rat.
1982,
Pubmed Dumont,
Characterization of non-opioid [3H]dynorphin A-(1-13) binding sites in the rat heart.
1993,
Pubmed Faden,
Dynorphin increases extracellular levels of excitatory amino acids in the brain through a non-opioid mechanism.
1992,
Pubmed Gispen,
Interaction between ACTH fragments, brain opiate receptors and morphine-induced analgesia.
1976,
Pubmed Hooke,
Dynorphin A modulates acute and chronic opioid effects.
1995,
Pubmed Miura,
Dynorphin binds to neuropeptide Y and peptide YY receptors in human neuroblastoma cell lines.
1994,
Pubmed Poggioli,
ACTH-(1-24) and alpha-MSH antagonize feeding behavior stimulated by kappa opiate agonists.
1986,
Pubmed Polgar,
Desensitization of melanotropin receptors in COS-7 cells.
1996,
Pubmed Quillan,
Structure-based search for peptide ligands that cross-react with melanocortin receptors.
1996,
Pubmed
,
Xenbase Quillan,
Combinatorial diffusion assay used to identify topically active melanocyte-stimulating hormone receptor antagonists.
1995,
Pubmed
,
Xenbase Shukla,
Non-opioid effects of dynorphins: possible role of the NMDA receptor.
1994,
Pubmed Stanfa,
Spinal opioid systems in inflammation.
1995,
Pubmed Székely,
Attenuation of morphine tolerance and dependence by alpha-melanocyte stimulating hormone(alpha-MSH).
1979,
Pubmed Takemori,
Suppression by dynorphin A and [des-Tyr1]dynorphin A peptides of the expression of opiate withdrawal and tolerance in morphine-dependent mice.
1993,
Pubmed Walker,
Dynorphin (1-17): lack of analgesia but evidence for non-opiate electrophysiological and motor effects.
,
Pubmed Walker,
Induction of analgesia by central administration of ORG 2766, an analog of ACTH4--9.
1981,
Pubmed Walker,
Nonopiate effects of dynorphin and des-Tyr-dynorphin.
1982,
Pubmed Weng,
Studies on neuropeptide Y receptors in a mouse adrenocortical cell line.
1995,
Pubmed Zhang,
Identification of dynorphins as endogenous ligands for an opioid receptor-like orphan receptor.
1995,
Pubmed
,
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