Functional characterization of the modified melanocortin peptides responsible for ligand selectivity at the human melanocortin receptors.


:The melanocortin system plays an important role in energy homeostasis as well as skin pigmentation, steroidogenesis and exocrine gland function. In this study, we examined eight Ac-His-Phe-Arg-Trp-NH(2) tetrapeptides that were modified at the Phe position and pharmacologically characterized their activities at the human MCR wild-types and their mutants. Our results indicate that at the hMC1R, all D stereochemical modified residues at the Phe position of peptides increase cAMP production in a dose-dependent manner. At the hMC3R, the DPhe peptide dose dependently increases cAMP production but all other three tetrapeptides were not. At the hMC4R, both the DPhe and DNal(1') peptides induce cAMP production. However, both DTyr and DNal(2') were not able to induce cAMP production. Further studies indicated that at the hMC1R M128L mutant receptor, the all D-configured tetrapeptides reduce their potencies as compared to that of hMC1R wild-type. However, at the hMC3R and hMC4R L165M and L133M mutant receptors, the DNal(2') and DTyr tetrapeptides possess agonist activity. These findings indicate that DPhe in tetrapeptide plays an important role in ligand selectivity and specific residue TM3 of the melanocortin receptors is crucial for ligand selectivity.






Chen M,Georgeson KE,Harmon CM,Haskell-Luevano C,Yang Y




Has Abstract


2006-11-01 00:00:00
















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    abstract::Peptides are an important class of molecules with diverse biological activities. Many endogenous peptides, especially neuropeptides and peptide hormones, play critical roles in development and regulating homeostasis. Furthermore, as drug candidates their high receptor selectivity and potent binding leads to reduced of...


    pub_type: 杂志文章,评审


    authors: Apostol CR,Hay M,Polt R

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  • Relationship between gallbladder bile concentration and motility in conscious dogs: role of cholecystokinin.

    abstract::The relationship between gallbladder (GB) bile concentration and motility was studied in conscious dogs. The 12-h GB bile concentrations between meals could be divided into three periods: diluting, minimum, and concentrating periods. During the diluting period, inhibition of GB contractions by a CCKA receptor antagoni...


    pub_type: 杂志文章


    authors: Muramatsu S,Sonobe K,Mizumoto A,Yamada T,Itoh Z

    更新日期:1997-01-01 00:00:00

  • Dynorphin increases in the dorsal spinal cord in rats with a painful peripheral neuropathy.

    abstract::It is known that painful tissue injury evokes an increase in dynorphin in spinal neurons. It is not known, however, whether dynorphinergic systems respond similarly to the pain that accompanies peripheral neuropathy. Radioimmunoassays and immunocytochemistry were used to evaluate changes in dynorphin A(1-8) in the spi...


    pub_type: 杂志文章


    authors: Kajander KC,Sahara Y,Iadarola MJ,Bennett GJ

    更新日期:1990-07-01 00:00:00

  • The first pacifastin elastase inhibitor characterized from a blood sucking animal.

    abstract::Pacifastin-like protease inhibitors belong to a recent classified protease inhibitor family and they are the smallest protease inhibitors described in animals. In this work, we purified and characterized, for the first time, two neutrophil elastase inhibitors belonging to the pacifastin family from the blood sucking i...


    pub_type: 杂志文章


    authors: de Marco R,Lovato DV,Torquato RJ,Clara RO,Buarque DS,Tanaka AS

    更新日期:2010-07-01 00:00:00

  • Neuronal cell lines expressing PC5, but not PC1 or PC2, process Pro-CCK into glycine-extended CCK 12 and 22.

    abstract::Endocrine tumor cells in culture and in vitro cleavage assays have shown that PC1 and PC2 are capable of processing pro-CCK into smaller, intermediate and final, bioactive forms. Similar studies have shown that PC5 has the ability to process a number of propeptides. Here, we use GT1-7 (mouse hypothalamic) and SK-N-MC ...


    pub_type: 杂志文章


    authors: Cain BM,Vishnuvardhan D,Beinfeld MC

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  • Purification and characterization of a novel antimicrobial peptide from Brevibacillus laterosporus strain A60.

    abstract::A novel antimicrobial peptide, with molecular mass of 1602.0469Da, produced by Brevibacillus laterosporus strain A60 was isolated and purified from the soil of mango plants. The purification procedure consisted of ammonium sulfate precipitation, cation exchange chromatography on an HiTrap SP HP column, thin layer chro...


    pub_type: 杂志文章


    authors: Zhao J,Guo L,Zeng H,Yang X,Yuan J,Shi H,Xiong Y,Chen M,Han L,Qiu D

    更新日期:2012-02-01 00:00:00

  • Endothelin-3 applied to the brain evokes opposite effects on bile secretion mediated by a central nitric oxide pathway.

    abstract::We sought to establish Endothelin (ET-3) role in the central regulation of bile secretion in the rat. The intracerebroventricular (icv) injection of ET-3 evoked a cholestatic or a choleretic effect depending on the administered dose. Lower doses increased bile flow and bicarbonate excretion, whereas higher doses decre...


    pub_type: 杂志文章


    authors: Rodríguez MR,Sabbatini ME,Santella G,Dabas P,Villagra A,Vatta MS,Bianciotti LG

    更新日期:2005-07-01 00:00:00

  • Differential sensitivity to neurotensin-induced hypothermia, but not analgesia, in Fischer and Lewis rats.

    abstract::Neurotensin (NT) produces behavioral and physiological effects, including analgesia and hypotheria, when administered into the CNS. Fischer and Lewis rats exhibit differential behavioral responses to central NT receptor activation. To further characterize these differences, we assessed central NT-induced analgesia and...


    pub_type: 杂志文章


    authors: Bauco P,Rompré PP

    更新日期:2003-08-01 00:00:00

  • Apelin alleviates diabetes-associated endoplasmic reticulum stress in the pancreas of Akita mice.

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    pub_type: 杂志文章


    authors: Chen H,Zheng C,Zhang X,Li J,Li J,Zheng L,Huang K

    更新日期:2011-08-01 00:00:00

  • A thaumatin-like antifungal protein from the emperor banana.

    abstract::A 20-kDa protein with substantial N-terminal sequence homology to thaumatin-like proteins was isolated from ripe fruits of the emperor banana, Musa basjoo cv. 'emperor banana'. The isolation procedure entailed (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, and affinity chromatography on ...


    pub_type: 杂志文章


    authors: Ho VS,Wong JH,Ng TB

    更新日期:2007-04-01 00:00:00

  • Neurotensin-induced miosis: the role of dopaminergic pathways.

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    pub_type: 杂志文章


    authors: Tassorelli C,Spampinato D,Caruso P,Cavaliere S,Micieli G,Drago F,Nappi G

    更新日期:1990-11-01 00:00:00

  • Neuropeptide Y in the recurrent mossy fiber pathway.

    abstract::In the epileptic brain, hippocampal dentate granule cells become synaptically interconnected through the sprouting of mossy fibers. This new circuitry is expected to facilitate epileptiform discharge. Prolonged seizures induce the long-lasting neoexpression of neuropeptide Y (NPY) in mossy fibers. NPY is released spon...


    pub_type: 杂志文章,评审


    authors: Nadler JV,Tu B,Timofeeva O,Jiao Y,Herzog H

    更新日期:2007-02-01 00:00:00

  • Exenatide and feeding: possible peripheral neuronal pathways.

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    pub_type: 杂志文章


    authors: Hunt JV,Washington MC,Sayegh AI

    更新日期:2012-02-01 00:00:00

  • Increased acyl ghrelin but decreased total ghrelin and unacyl ghrelin in Chinese Han people with impaired fasting glucose combined with impaired glucose tolerance.

    abstract::We assessed the plasma acyl ghrelin (AG), unacyl ghrelin (UAG), and total ghrelin (TGhr) levels in Chinese adults with pre-diabetes and newly diagnosed diabetes mellitus (NDDM) after an oral glucose tolerance test (OGTT), and abdominal subcutaneous fat area and visceral fat area (VFA) were measured. Fasting AG level w...


    pub_type: 杂志文章


    authors: Huang L,Tong Y,Zhang F,Yang Q,Li D,Xie S,Li Y,Cao H,Tang L,Zhang X,Tong N

    更新日期:2014-10-01 00:00:00

  • Structure-activity studies of alpha-melanotropin fragments on cAMP production in striatal slices.

    abstract::In this work, we characterized the active site in the alpha-melanotropin hormone (alpha-MSH) sequence responsible for the enhancement of cAMP production in incubated striatal slices by using different alpha-MSH fragments. We also analyzed the effects of the co-incubation of the SCH23390, a dopaminergic D(1) antagonist...


    pub_type: 杂志文章


    authors: Cecilia Cremer M,Silvina Sanchez M,Ester Celis M

    更新日期:2000-06-01 00:00:00

  • Interaction between hypothalamic peptides in a superfused pituitary cell system.

    abstract::Recently two hypothalamic releasing factors have been isolated, sequenced and synthesized: corticotropin-releasing factor (CRF) from sheep and rat hypothalami; and growth hormone-releasing factor (GH-RF) from tumors in human pancreas (hpGH-RF) and from rat hypothalami (rhGH-RF). Their biological potencies were tested ...


    pub_type: 杂志文章


    authors: Vigh S,Schally AV

    更新日期:1984-01-01 00:00:00

  • Ischemic-reperfused rat skeletal muscle: the effect of vasoactive intestinal peptide (VIP) on contractile force, oxygenation and antioxidant enzyme systems.

    abstract::The effect of vasoactive intestinal peptide (VIP) on the nerve-stimulated contraction, tissue oxygenation, lipid peroxidation and antioxidant enzymes activities-superoxide dismutase and catalase was investigated in the rat gastrocnemius muscle exposed to 4 h ischemia-4hr reperfusion. Ischemia caused significant decrea...


    pub_type: 杂志文章


    authors: Tunçel N,Erden S,Uzuner K,Altiokka G,Tunçel M

    更新日期:1997-01-01 00:00:00

  • Mechanisms involved in the somatostatin-induced contraction of vascular smooth muscle cells.

    abstract::In experimental models and in humans, somatostatin (SRIF) is able to contract certain vascular structures. The present experiments were designed to assess the capacity of SRIF to contract cultured rat aortic vascular smooth muscle cells (VSMC), and to analyze the possible mechanisms involved. Cells incubated with SRIF...


    pub_type: 杂志文章


    authors: Torrecillas G,Medina J,Díez-Marqués ML,Rodríguez-Puyol D,Rodríguez-Puyol M

    更新日期:1999-01-01 00:00:00

  • Characterization of a new bioactive peptide from Potamotrygon gr. orbignyi freshwater stingray venom.

    abstract::Brazilian freshwater stingrays, Potamotrygon gr. orbigyni, are relatively common in the middle-western regions of Brazil, where they are considered an important public health threat. In order to identify some of their naturally occurring toxin peptides available in very low amounts, we combine analytical protocols suc...


    pub_type: 杂志文章


    authors: Conceição K,Santos JM,Bruni FM,Klitzke CF,Marques EE,Borges MH,Melo RL,Fernandez JH,Lopes-Ferreira M

    更新日期:2009-12-01 00:00:00

  • Antimicrobial activity of polycationic peptides.

    abstract::The in vitro activity of six polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, nisin, and ranalexin, were evaluated against several clinical isolates of gram-positive and gram-negative aerobic bacteria, yeasts, Pneumocystis carinii and Cryptosporidium parvum, by using microbroth dilution method...


    pub_type: 杂志文章


    authors: Giacometti A,Cirioni O,Barchiesi F,Del Prete MS,Scalise G

    更新日期:1999-11-01 00:00:00

  • Short-term behavioral effects of posterior pituitary peptides in mice.

    abstract::The acute behavioral effects of some neurohypophyseal hormones after intracerebroventricular injection in mice were examined. The effects, consisting mainly of a dose-dependent stimulation of certain behaviors, were demonstrated in three different behavioral tests. The type of the induced behaviors was dependent on th...


    pub_type: 杂志文章


    authors: Meisenberg G

    更新日期:1981-04-01 00:00:00

  • RISK pathway is involved in oxytocin postconditioning in isolated rat heart.

    abstract::The reperfusion injury salvage kinase (RISK) pathway is a fundamental signal transduction cascade in the cardioprotective mechanism of ischemic postconditioning. In the present study, we examined the cardioprotective role of oxytocin as a postconditioning agent via activation of the RISK pathway (PI3K/Akt and ERK1/2)....


    pub_type: 杂志文章


    authors: Polshekan M,Jamialahmadi K,Khori V,Alizadeh AM,Saeidi M,Ghayour-Mobarhan M,Jand Y,Ghahremani MH,Yazdani Y

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  • VIP regulation of a human pancreatic cancer cell line: Capan-1.

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    pub_type: 杂志文章


    authors: Ruellan C,Scemama JL,Clerc P,Fagot-Revurat P,Clemente F,Ribet A

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  • Naltrexone, naltrindole, and CTOP block cocaine-induced sensitization to seizures and death.

    abstract::I.c.v. injection for 9 days of either naltexone (NTX) (5, 10, 20, 40 micrograms/rat) or a selective mu peptide (CTOP) (0.125, 0.25, 0.5, 1, 3, 6 micrograms/rat) or delta (naltrindole) (NLT) (5, 10, 20 micrograms/rat) subtype opioid receptor antagonist affected sensitization to cocaine (COC) (50 mg/kg, i.p.) administer...


    pub_type: 杂志文章


    authors: Braida D,Paladini E,Gori E,Sala M

    更新日期:1997-01-01 00:00:00

  • Modulation of active avoidance behavior of rats by ICV administration of CGRP antiserum.

    abstract::The effects of ICV administration of CGRP antiserum on active avoidance behavior were studied in rats. CGRP antiserum dilutions of 1:5, 1:10, 1:20, and 1:40 facilitated the extinction of active avoidance responses in a platform-jumping situation in the 3- and 6-h tests. In the 24-h test, only the CGRP antiserum diluti...


    pub_type: 杂志文章


    authors: Kovcs A,Telegdy G

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  • Effect of epidermal growth factor (EGF) on [3H]TdR incorporation into DNA in ad lib fed and fasted CD2F1 mice.

    abstract::The effect of EGF on the incorporation of [3H]TdR into DNA (DNA synthesis) was determined in the esophagus, liver, pancreas, and kidney in mice standardized to 12 hours (hr) of light alternating with 12 hr of darkness. A question asked was whether intraperitoneally administered EGF could alter the circadian patterns o...


    pub_type: 杂志文章


    authors: Scheving LA,Tsai TH,Scheving LE,Hoke WS

    更新日期:1987-03-01 00:00:00

  • Neurotrophin-3 and neurotrophin receptor immunoreactivity in peptidergic enteric neurons.

    abstract::In the rat small intestine, neurotrophin-3 immunoreactivity was identified in ganglion cells and in processes mostly innervating the mucosa and occasionally the muscle layer and vasculature. The vast majority of neurotrophin-3 immunoreactive neurons contained vasoactive intestinal polypeptide (VIP), but not substance ...


    pub_type: 杂志文章


    authors: De Giorgio R,Arakawa J,Wetmore CJ,Sternini C

    更新日期:2000-09-01 00:00:00

  • Selective, physiological transport of insulin across the blood-brain barrier: novel demonstration by species-specific radioimmunoassays.

    abstract::Insulin in blood is thought to cross the blood-brain barrier (BBB) to act within the brain to help control appetite. We examined the ability of blood-borne insulin to cross the BBB. Human insulin was infused for 48 h subcutaneously at several doses into mice and the amount of human and murine insulin in serum and brai...


    pub_type: 杂志文章


    authors: Banks WA,Jaspan JB,Kastin AJ

    更新日期:1997-01-01 00:00:00

  • Synthetic peptides related to the dermorphins. II. Synthesis and biological activities of new analogues.

    abstract::A new series of analogues of the potent opiate-like peptides dermorphins (mainly tetra- and pentapeptides) were synthesized in order to better evaluate the structure-activity relationships. Relative potencies were referred to dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), the prototype of this class of frog skin pe...


    pub_type: 杂志文章


    authors: Melchiorri P,Erspamer GF,Erspamer V,Guglietta A,De Castiglione R,Faoro F,Perseo G,Piani S,Santangelo F

    更新日期:1982-09-01 00:00:00

  • Molecular diversity and evolution of myticin-C antimicrobial peptide variants in the Mediterranean mussel, Mytilus galloprovincialis.

    abstract::Mussels have diverse groups of cysteine rich, cationic antimicrobial peptides (AMPs) (defensins, mytilins, myticins, and mytimycin) that constitute an important component of their innate immune defence. Despite the identification and characterization of these AMPs in mussels, the underlying genetic mechanisms that mai...


    pub_type: 杂志文章


    authors: Padhi A,Verghese B

    更新日期:2008-07-01 00:00:00