Peptides (v.29, #4)
Announcement - Japan (V).
Editorial Board (CO2).
Mapping IgE-binding epitopes of Ric c 1 and Ric c 3, allergens from Ricinus communis, by mast cell degranulation assay by S.P. Felix; R.O. Mayerhoffer; R.A. Damatta; M.A. Verícimo; V.V. Nascimento; O.L.T. Machado (497-504).
Ric c 1 and Ric c 3 are the major castor bean allergens. In order to identify continuous IgE-epitopes in Ric c 1 and Ric c 3, pools of sera from rats immunized with a pool of 2S albumin from these seeds, Ric c 1 and Ric c 3 overlapping synthetic peptides, were used to screen for IgE-binding epitopes. The allergenic properties were monitored by mast cell degranulation assays, histamine quantification and human-IgE binding. Large and small chains isolated from these proteins present allergenic properties. Four continuous epitopes were identified in Ric c 3 and two in Ric c 1. This knowledge may allow the induction of protective antibody responses to antagonize the IgE recognition.
Keywords: Castor bean; 2S albumin; Ricinus communis; Ric c 1; Ric c 3; CB-1A;
Identification of novel semenogelin I-derived antimicrobial peptide from liquefied human seminal plasma by Hui Zhao; Wen-Hui Lee; Ji-Hong Shen; Hong Li; Yun Zhang (505-511).
Semenogelin I (SgI) is one of the most abundant proteins in human seminal plasma. SgI plays a key role in sperm coagulation and spermatozoon immobilization. In addition, SgI and/or its proteolytic fragments are involved in regulating spermatozoon motility, capacitation and inhibin-like activity. However, little is known about the antibacterial activity of SgI-derived peptides. By a combination of ion-exchange, gel filtration and high-performance liquid chromatography, peptides from liquefied human seminal plasma from 40 healthy donors were isolated and characterized. N-terminal amino-acid sequencing and fast atom bombardment mass spectrometry revealed that four isolated peptides were SgI-derived, namely SgI-29 (85–113), SgI-46 (85–130), SgI-47 (85–131) and SgI-52 (85–136). Interestingly, SgI-29, SgI-46 and SgI-47 are newly identified SgI-derived peptides. Antimicrobial activity assay results indicated that synthesized SgI-29 had strong antibacterial activity toward various bacterial strains. Our results indicate that SgI can be digested into small fragments like newly identified SgI-29, SgI-46 and SgI-47 and may have diversified functions.
Keywords: Antimicrobial peptides; Semenogelin I; Seminal plasma;
Characterization and functional recovery of a novel antimicrobial peptide (CECdir–CECret) from inclusion bodies after expression in Escherichia coli by Paulina Schmitt; Luis Mercado; Mauricio Díaz; Fanny Guzmán; Gloria Arenas; Sergio H. Marshall (512-519).
CECdir–CECret is a novel non-toxic doublet 8.5 kDa peptide representing the natural coding sequence of the antimicrobial peptide Cecropin A from Drosophila melanogaster fused in-frame to its own inverted version. Expression of this cloned doublet peptide in Escherichia coli, yielded peptides that were mostly packaged into inclusion bodies. The new molecule was purified, solubilized and refolded, through a standard guanidine-based procedure. The recovered refolded peptides were then characterized by HPLC chromatography, MALDI-TOF-mass spectrometry and peptide sequencing, and finally evaluated for their antimicrobial potential. The novel doublet peptide CECdir–CECret, displays an enhanced in vitro antimicrobial activity and action spectrum in comparison to the monomer Cecropin A.
Keywords: Inclusion bodies; Refolding procedure; Antibacterial peptides; Cecropin;
Temporin A is effective in MRSA-infected wounds through bactericidal activity and acceleration of wound repair in a murine model by Oriana Simonetti; Oscar Cirioni; Gaia Goteri; Roberto Ghiselli; Wojciech Kamysz; Elzbieta Kamysz; Carmela Silvestri; Fiorenza Orlando; Claudia Barucca; Alessandro Scalise; Vittorio Saba; Giorgio Scalise; Andrea Giacometti; Annamaria Offidani (520-528).
We investigated the effect of topical temporin A in the management of methicillin-resistant strain of Staphylococcus aureus (MRSA)-infected experimental surgical wounds in mice. The wound, cut through the panniculus carnosus of BALB/c mice, was inoculated with 5 × 107 colony-forming units of MRSA. Mice were treated with Allevyn, temporin A-soaked Allevyn, Allevyn and daily intraperitoneal teicoplanin (7 mg/kg), temporin A-soaked Allevyn and daily intraperitoneal teicoplanin. Main outcome measurements were: quantitative bacterial culture, histological examination with assessment of micro-vessel density and of vascular endothelial growth factor (VEGF) expression in tissue sections, and VEGF plasma levels alike. Treatment with temporin-A associated with teicoplanin injection significantly reduced bacterial load to 0.85 × 101 ± 0.1 × 101 CFU/ml. Histological examination showed that infected mice receiving temporin A-soaked Allevyn (with or without teicoplanin) had a higher degree of granulation tissue formation and collagen deposition compared to the other treated groups. A significant increase in serum VEGF expression was observed in mice receiving temporin A topically and temporin A topically associated with intraperitoneal teicoplanin. In conclusion our results demonstrated that temporin A is effective in the management of infected wounds, by a significant bacterial growth inhibition and acceleration of wound repair process.
Keywords: Temporin A; MRSA infection; Wound repair; Teicoplanin; VEGF;
A novel antimicrobial peptide from amphibian skin secretions of Odorrana grahami by Qiaolin Che; Yu Zhou; Hailong Yang; Jianxu Li; Xueqing Xu; Ren Lai (529-535).
A novel antimicrobial peptide named odorranain-NR was identified from skin secretions of the diskless odorous frog, Odorrana grahami. It is composed of 23 amino acids with an amino acid sequence of GLLSGILGAGKHIVCGLTGCAKA. Odorranain-NR was classified into a novel family of antimicrobial peptide although it shared similarity with amphibian antimicrobial peptide family of nigrocin. Odorranain-NR has an unusual intramolecular disulfide-bridged hexapeptide segment that is different from the intramolecular disulfide-bridged heptapeptide segment at the C-terminal end of nigrocins. Furthermore, the -AKA fragment at the C-terminal of odorranain-NR is also different from nigrocins. Three different cDNAs encoding two odorranain-NR precursors and only one mature odorranain-NR was cloned from the cDNA library of the skin of O. grahami. This peptide showed antimicrobial activities against tested microorganisms except Escherichia coli (ATCC25922). Its antimicrobial mechanisms were investigated by transmission electron microcopy. odorranain-NR exerted its antimicrobial functions by various means depending on different microorganisms.
Keywords: Amphibian; Antimicrobial peptide; Odorrana grahami; Innate immunity;
Novel peptide toxins from the sea anemone Stichodactyla haddoni by Tomohiro Honma; Shino Kawahata; Masami Ishida; Hiroshi Nagai; Yuji Nagashima; Kazuo Shiomi (536-544).
Four peptide toxins, SHTX I–III with crab-paralyzing activity and SHTX IV with crab lethality, were isolated from the sea anemone Stichodactyla haddoni and their primary structures elucidated by protein sequencing and cDNA cloning. SHTX I (new toxin, 28 residues), II (analogue of SHTX I, 28 residues) and III (Kunitz-type protease inhibitor, 62 residues) are potassium channel toxins and SHTX IV (48 residues) is a member of the type 2 sea anemone sodium channel toxins. The precursor protein of SHTX IV is composed of a signal peptide, propart and mature peptide, while the propart is missing in that of SHTX III. In addition to these four toxins, an epidermal growth factor-like peptide was detected in S. haddoni by RT-PCR.
Keywords: EGF-like peptide; Peptide toxin; Potassium channel toxicity; Sea anemone; Stichodactyla haddoni;
Characterization of neuropeptide F-like immunoreactivity in the blood-feeding hemipteran, Rhodnius prolixus by Ronald Gonzalez; Ian Orchard (545-558).
The invertebrate neuropeptide Y (NPY) homolog, neuropeptide F (NPF), has been characterized for a wide range of invertebrate phyla, including platyhelminthes, molluscs, and arthropods. Current hypotheses suggest that NPF may be capable of regulating responses to diverse external cues related to nutritional status and feeding. The qualitative and quantitative distribution of an NPF-like peptide in fifth instar Rhodnius prolixus was undertaken using an antiserum raised against Drosophila NPF. Immunohistochemistry reveals NPF-like immunoreactive neurons and processes in the central nervous system, stomatogastric nervous system and peripheral nervous system. The distribution of NPF-like immunoreactivity within the medial neurosecretory cells of the brain and neurohemal areas of the corpus cardiacum and dorsal vessel, suggests NPF may act as a neurohormone. Immunoreactive processes are present over the surface of the hindgut and the immunoreactivity in these processes is greatly reduced in intensity 24 h post-feeding. The quantification of partially purified NPF-like material in the CNS of R. prolixus was conducted by HPLC fractionation and radioimmunoassay. The results suggest that NPF-like material is present in fifth instar R. prolixus and likely released into the hemolymph following a blood meal.
Keywords: Insect; Immunoreactivity; Hindgut; Feeding; Neuropeptide F; Neuropeptide Y;
Enterostatin (APGPR) suppresses the analgesic activity of morphine by a CCK-dependent mechanism by Yasuyuki Takenaka; Tomoko Shimano; Yuko Yamada; Mariko Yoshida; Kousaku Ohinata; Masaaki Yoshikawa (559-563).
Enterostatin (APGPR) found in the gastrointestinal tract and brain is an anorectic pentapeptide. We found that APGPR inhibited morphine-induced analgesia after intracerebroventricular administration in mice at a dose of 10 nmol/mouse. The anti-analgesic effect of APGPR was inhibited by pretreatment with lorglumide and LY225910, antagonists for cholecystokinin 1 (CCK1) and cholecystokinin 2 (CCK2) receptors, respectively. The anti-analgesic effect of APGPR may be mediated by CCK release, since APGPR does not have affinity for CCK receptors.
Keywords: Enterostatin; APGPR; Anti-analgesia; CCK1 receptor; CCK2 receptor;
The endogenous CCK mediation of electroacupuncture stimulation-induced satiety in rats by Sun Kwang Kim; Hyunsu Bae; Giseog Lee; Hyunjeong Jeong; Hyun Su Woo; Jae-Bok Han; Yangseok Kim; Hyejung Lee; Min-Kyu Shin; Moo-Chang Hong; Young-Ho Jin; Byung-Il Min (564-570).
A major satiety hormone, cholecystokinin (CCK) is well known to be released by electroacupuncture (EA) stimulation at certain body sites which elicits profound psychophysiological responses. Previous clinical and animal studies have shown that EA stimulation reduces food intake and body weight in both normal and obese subjects. The aim of the present study was to elucidate the satiety effect of EA stimulation and its mechanism related to CCK in rats. Here we show that EA stimulation at “Zusanli” (ST36) acupoint significantly reduced 30-min and 60-min food intake in 48-h fasted Sprague–Dawley rats, and such effect was reversed by a lorglumide (CCK-1 receptor antagonist, 10 mg/kg, i.p.) pretreatment. The ST36 EA stimulation-induced satiety was not observed in CCK-1 receptor knockout, Otsuka Long-Evans Tokushima Fatty rats, but in their controls, Long-Evans Tokushima Otsuka rats. Subdiaphragmatic vagotomy also blocked the satiety effect of ST36 EA stimulation in Sprague-Dawley rats. These results suggest that ST36 EA stimulation elicits satiety in rats and this is mediated by the endogenous CCK signaling pathway.
Keywords: Cholecystokinin; Electroacupuncture; Satiety; Lorglumide; Otsuka Long-Evans Tokushima Fatty rat; Vagotomy;
PACAP is transiently expressed in anterior pituitary gland of rats: In situ hybridization and cell immunoblot assay studies by Andrea Heinzlmann; Eszter Kirilly; Kinga Meltzer; Enikő Szabó; Akemichi Baba; Hitoshi Hashimoto; Katalin Köves (571-577).
In this work the expression of PACAP (pituitary adenylate cyclase activating polypeptide) in rat anterior pituitary was demonstrated for the first time using in situ hybridization. The number of cells showing PACAP signal in intact male rats was negligible similarly to that of diestrous rats. In proestrous rats sacrificed at 10 h there was a moderate increase in the expression and after a decrease at 16 h and 18 h, there was a transient peak at 20 h and then the number of labeled cells was declined again (22 h). In the cell immunoblot assay study it was observed that the number of PACAP blot forming (PACAP releasing) cells in an anterior pituitary cell culture changed according to a similar pattern as the number of PACAP expressing cells. The number of blots was also the highest when the animals were sacrificed in the evening of proestrus at 20 h. The results obtained by in situ hybridization and cell immunoblot assay well correlate with each other. The above-mentioned results support our hypothesis that the enhanced expression and secretion of PACAP in the pituitary gland may be involved in ceasing the LH surge.
Keywords: Cell culturing; Immunohistochemistry; Ovarian cyclicity;
Inhibition of β-amyloid peptide aggregation and neurotoxicity by α-d-mannosylglycerate, a natural extremolyte by Jungki Ryu; Mathumai Kanapathipillai; Georg Lentzen; Chan Beum Park (578-584).
The aggregation of soluble β-amyloid (Aβ) peptide into oligomers/fibrils is one of the key pathological features in Alzheimer's disease (AD). The use of naturally occurring small molecules for inhibiting protein aggregation has recently attracted many interests due to their effectiveness for treating protein folding diseases such as AD, Parkinson's, Huntington's disease, and other amyloidosis diseases. α-d-Mannosylglycerate (MG), a natural extremolyte identified in microorganisms growing under extremely high temperatures up to 100 °C, had been shown to protect proteins against various stress conditions such as heat, freezing, thawing, and drying. Here, we report the effectiveness of MG on the suppression of Alzheimer's Aβ aggregation and neurotoxicity to human neuroblastoma cells. According to our study – carried out by using thioflavin-T induced fluorescence, atomic force microscopy, and cell viability assay – MG had significant inhibitory effect against Aβ amyloid formation and could reduce the toxicity of amyloid aggregates to human neuroblastoma cells while MG itself was innocuous to cells. On the other hand, the structural analogs of MG such as α-d-mannosylglyceramide, mannose, methylmannoside, glycerol, showed negligible effect on Aβ aggregate formation. The results suggest that MG could be a potential drug candidate for treating Alzheimer's disease.
Effect of motilin on the discharge of rat hippocampal neurons responding to gastric distension and its potential mechanism by Luo Xu; Xiangrong Sun; Inge Depoortere; Jiang Lu; Feifei Guo; Theo Louis Peeters (585-592).
The study aims to find the effect of motilin on neuronal activity of gastric distension-responsive neurons in rat hippocampus and its possible mechanism. Single unit discharges in the hippocampal CA1 region were recorded extracellularly by means of four-barrel glass micropipettes in anesthetized rats and the expression of nNOS in hippocampus was observed by fluo-immunohistochemistry staining. Of the 171 recorded neurons, 76.0% were GD-excitatory (GD-E) neurons and 24.0% were GD-inhibited (GD-I) neurons. The 57.6% of GD-E neurons showed an excitatory response to motilin and the same effect was observed in 51.7% GD-I neurons. However, when NOS inhibitor nitro-l-arginine methyl ester (l-NAME) was administrated previously, the followed motilin-induced excitatory responsiveness of GD-responsive neurons was reduced. In contrast, discharge activity of GD-responsive neurons with motilin was enhanced by pretreatment of NO precursor l-arginine. The expression of nNOS-IR positive neurons was significantly increased in CA1 after administration of motilin. Our findings suggested that motilin excited the GD-responsive neurons in the hippocampal CA1 region and the excitatory effect of motilin may be mediated by the endogenous NO.
Keywords: Motilin; NO; CA1-hippocampus; Gastric distension-responsive neurons;
Increased leptin expression selectively in the hypothalamus suppresses inflammatory markers CRP and IL-6 in leptin-deficient diabetic obese mice by Michael G. Dube; Rita Torto; Satya P. Kalra (593-598).
Low-grade systemic inflammation, as indicated by increased circulating levels of inflammatory markers CRP and IL-6, is linked to increased risks for cardiovascular diseases (CVD) and diabetes mellitus in obese subjects. Whereas hyperleptinemia in obesity are associated with increased CRP and IL-6 release, the hypothalamic versus peripheral site of leptin action has not been ascertained. The effects of increased leptin supply selectively in the hypothalamus by gene therapy on pro-inflammatory CRP and IL-6 levels and on markers of diabetes in the circulation of ob/ob mice displaying either age-related or dietary obesity were assessed. A recombinant adeno-associated viral vector encoding either green-fluorescent protein (control) or leptin gene was injected intracerebroventricularly. Five weeks later, one-half of each of the vector groups was switched to high-fat diet consumption and the other half continued to consume regular low-fat chow diet. Body weight and visceral white adipose tissue were drastically reduced and hyperinsulinemia and hyperglycemia were abrogated by leptin gene therapy, independent of the dietary fat content. The elevated plasma CRP and IL-6 levels seen in obese ob/ob mice receiving the control vector, regardless of the fat content of the diet, were markedly suppressed by increased hypothalamic leptin in both groups. The results show for the first time that leptin deficiency elevates and reinstatement of leptin selectively in the hypothalamus suppresses the release of pro-inflammatory biomarkers, a response likely to alleviate CVD associated with obesity.
Keywords: C-reactive protein; Interleukin-6; Inflammation; Gene therapy; Obesity;
Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: Comparison with C-reactive protein and adiponectin by Hidenori Nishida; Takeshi Horio; Yoshihiko Suzuki; Yoshio Iwashima; Kei Kamide; Kenji Kangawa; Yuhei Kawano (599-605).
This study investigated the predictive power of plasma adrenomedullin (AM) for future cardiovascular (CV) events. In 121 patients with multiple CV risk factors and/or disease, plasma concentrations of AM, high sensitive C-reactive protein (hs-CRP), and adiponectin were measured. During follow-up periods (mean, 3.5 years) after the baseline assessment, 28 patients newly experienced CV events such as stroke/transient ischemic attack, acute coronary syndrome, and congestive heart failure. The plasma level of AM, but not hs-CRP or adiponectin, was significantly higher in patients who had CV events than in event-free subjects. When the patients were divided into three groups by tertiles of basal levels of AM (<10.1, 10.1–13.1, and ≥13.1 fmol/mL), cumulative event-free rates by the Kaplan–Meier method were decreased according to the increase in basal AM levels (83.2%, 68.6%, and 52.8% in the lowest, middle, and highest tertiles of AM, respectively; log-rank test, P = 0.033). By univariate Cox regression analysis, previous coronary artery disease, creatinine clearance, and plasma AM and hs-CRP levels were significantly associated with CV events during follow-up. Among these possible predictors, high plasma AM (P = 0.004) and low creatinine clearance (P = 0.043) were independent determinants for morbidity in multivariate analysis. These findings indicate that plasma AM is a powerful independent predictor of future CV events in high-risk patients, suggesting its predictive value is superior to that of hs-CRP or adiponectin.
Keywords: Adrenomedullin; C-reactive protein; Adiponectin; Cardiovascular disease; Morbidity;
Lack of direct interaction between enalaprilat and the kinin B1 receptors by Guillaume Morissette; Jean-Philippe Couture; Anik Désormeaux; Albert Adam; François Marceau (606-612).
It has been recently proposed that the second extracellular loop of the human bradykinin (BK) B1 receptor (B1R) contains a conserved HExxH motif also present in peptidases possessing a Zn2+ prosthetic group, such as angiotensin converting enzyme (ACE), and that ACE inhibitors directly activate B1R signaling in endothelial cells. However, the binding of ACE inhibitors to the B1Rs has never been directly evaluated. Information about binding of a radiolabeled inhibitor to natural or recombinant ACE in intact cells (physiologic ionic composition) was also collected. We used the tritiated form of an ACE inhibitor previously proposed to activate the B1R, enalaprilat, to address these questions using recombinant human B1Rs and naturally expressed or recombinant ACE. [3H]Lys-des-Arg9-BK bound to the human recombinant B1Rs with high affinity (K D 0.35 nM) in HEK 293a cells. [3H]Enalaprilat (0.25–10 nM) did not bind to cells expressing recombinant human B1R, but bound with a subnanomolar affinity to recombinant ACE or to naturally expressed ACE in human umbilical vein endothelial cells. The radioligand was further validated using a binding competition assay that involved unlabeled ACE inhibitors or their prodrug forms in endothelial cells. Membranes of HEK 293a cells that expressed B1Rs did not hydrolyze hippuryl-glycylglycine (an ACE substrate). Enalaprilat did not stimulate calcium signaling in HEK 293a cells that expressed B1Rs. A typical ACE inhibitor did not bind to nor stimulate the human B1Rs; nevertheless, several other indirect mechanisms could connect ACE inhibition to B1R stimulation in vivo.
Keywords: Enalaprilat; Bradykinin B1 receptor; Angiotensin converting enzyme; Binding assay;
Regulation of stretch-activated ANP secretion by chloride channels by Jeong Hee Han; Guang Yi Bai; Jae-Hyeong Park; Kuichang Yuan; Woo Hyun Park; Sung Zoo Kim; Suhn Hee Kim (613-621).
This study was aimed to define roles of stretch-activated ion channels (SACs), especially Cl− channels, in regulation of atrial natriuretic peptide (ANP) secretion using isolated perfused beating atria. The volume load was achieved by elevating height of outflow catheter connected to isolated rat atria and the pressure load was achieved by decreasing diameter of outflow catheter. Both methods increased atrial contractility similarly although volume load was different (736 μl for volume load vs. 129 μl for pressure load). Atrial stretch by volume load markedly increased ECF translocation and ANP secretion but the pressure load slightly increased. The ANP secretion was positively correlated to workload generated by volume or pressure load. Treatment of atria with gadolinium, a blocker for SACs, attenuated the ECF translocation and the ANP secretion induced by volume load. A blocker for Ca2+-activated Cl− channel, niflumic acid (NFA), accentuated the ANP secretion induced by volume load whereas a blocker for swelling-activated Cl− channel, diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS), attenuated the ANP secretion. The ANP secretion of hypertrophied atria by volume load was markedly reduced and the augmented effect of NFA on volume load-induced ANP secretion was not observed. These results indicate that Cl− channels may differently regulate stretch-activated ANP secretion.
Keywords: Stretch; Stretch-activated channel; Cl− channel; Atrium; Atrial natriuretic peptide; Hypertrophy;
Expression of natriuretic peptide-activated guanylate cyclases by cholinergic and dopaminergic amacrine cells of the rat retina by Essam Mohamed Abdelalim; Chiaki Masuda; Ikuo Tooyama (622-628).
Recently, the natriuretic peptides were detected in the cholinergic and dopaminergic amacrine cells of the retina. We performed immunofluorescence labeling of rat retinal sections to examine the immunoreactivity of natriuretic peptide-activated guanylate cyclases (NPR-A and NPR-B) in the rat retina, in particular whether they were localized to dopaminergic and cholinergic amacrine cells. NPR-A and NPR-B immunoreactivity was detected in several layers of the retina including amacrine cells. In amacrine cells, both NPR-A and NPR-B were co-localized with tyrosine hydroxylase, a marker of dopaminergic cells. NPR-B, but not NPR-A, was localized to amacrine cells expressing choline acetyltransferase (ChAT), a marker of cholinergic cells. These findings suggest that natriuretic peptides have different regulatory systems in dopaminergic and cholinergic amacrine cells in rat retina.
Keywords: NPR-A; NPR-B; Choline acetyltransferase; Tyrosine hydroxylase; Immunofluorescence;
Rubimetide (Met-Arg-Trp) derived from Rubisco exhibits anxiolytic-like activity via the DP1 receptor in male ddY mice by Hui Zhao; Kousaku Ohinata; Masaaki Yoshikawa (629-632).
In this study, we found that Met-Arg-Trp (rubimetide), which had been isolated as a hypotensive peptide from a pepsin–pancreatin digest of spinach ribulose bisphosphate carboxylase/oxygenase (Rubisco), has anxiolytic-like activity in the elevated plus-maze test at a dose of 0.1 mg/kg (i.p.) or 1.0 mg/kg (p.o.) in mice with p < 0.01 and p < 0.05, respectively. The anxiolytic-like activity of rubimetide (0.1 mg/kg, i.p.) was blocked by BW A868C (60 μg/kg, i.p.), an antagonist for the DP1 receptor, suggesting the anxiolytic-like activity of rubimetide is mediated by prostaglandin D2 and the DP1 receptor.
[Dmt1, d-1-Nal3]morphiceptin, a novel opioid peptide analog with high analgesic activity by Jakub Fichna; Jean-Claude do-Rego; Nga N. Chung; Jean Costentin; Peter W. Schiller; Anna Janecka (633-638).
The morphiceptin-derived peptide [Dmt1, d-1-Nal3]morphiceptin, labeled μ-opioid receptor (MOP) with very high affinity and selectivity in the receptor binding assays. In the mouse hot plate test, [Dmt1, d-1-Nal3]morphiceptin given intracerebroventricularly (i.c.v.) produced profound supraspinal analgesia, being approximately 100-fold more potent than the endogenous MOP receptor ligand, endomorphin-2. The antinociceptive effect of this new analog lasted up to 120 min. Thus, [Dmt1, d-1-Nal3]morphiceptin is an interesting and extraordinarily potent analgesic, raising the possibility of novel approaches in the design of clinically useful drugs for pain treatment.
Obestatin: Its physicochemical characteristics and physiological functions by Sheng-Qiu Tang; Qing-Yan Jiang; Yong-Liang Zhang; Xiao-Tong Zhu; Gang Shu; Ping Gao; Ding-Yuan Feng; Xiu-Qi Wang; Xiao-Ying Dong (639-645).
Obestatin, a novel 23 amino acid amidated peptide encoded by the same gene with ghrelin, was initially reported to reduce food intake, body weight gain, gastric emptying and suppress intestinal motility through an interaction with the orphan receptor GPR39. However, recently reports have shown that above findings had been questioned by several groups. Further studies explained that obestatin was involved in inhibiting thirst and anxiety, improving memory, regulating sleep, affecting cell proliferation, and increasing the secretion of pancreatic juice enzymes. We also identified that obestatin could stimulate piglet liver and adipose cell proliferation, and inhibit the secretion of IGF-I. According to the controversy over the effects and the cognate ligand of obestatin, here we provide the latest review on the structure, distribution and physiological functions of obestatin.
Keywords: Obestatin; Food intake; Gastric emptying; Ghrelin; GPR39; Cell proliferation; Strucure; Distribution;