Peptides (v.23, #8)

The fruiting bodies of the edible mushroom Pleurotus sajor-caju were extracted with an aqueous buffer and then subjected to affinity chromatography on Affi-gel Blue gel, ion exchange chromatography on DEAE-cellulose and gel filtration on Superdex 75. From the fraction of the extract adsorbed on Affi-gel Blue gel and unadsorbed on DEAE-cellulose, a 9.5 kDa peptide with an N-terminal sequence similar to ubiquitin was isolated with a yield of 0.25 mg/kg mushroom. The peptide inhibited cell-free translation with an IC50 of 30 nM. It exhibited a ribonuclease activity of 450 U/mg toward yeast transfer RNA. The activities were substantially more potent than those of previously isolated mushroom ubiquitin-like protein and peptide.
Keywords: Mushroom; Ubiquitin-like peptide; Ribonuclease; Translation-inhibitory;

Neuropeptide F and its expression in the yellow fever mosquito, Aedes aegypti by Dawn M Stanek; Jan Pohl; Joe W Crim; Mark R Brown (1367-1378).
A neuropeptide F (NPF) was isolated from an extract of adult Aedes aegypti mosquitoes based on its immunoreactivity in a radioimmunoassay for Drosophila NPF. After sequencing the peptide, cDNAs encoding the NPF were identified from head and midgut. These cDNAs encode a prepropeptide containing a 36 amino acid peptide with an amidated carboxyl terminus, and its sequence shows it to be a member of the neuropeptide F/Y superfamily. Immunocytochemistry and Northern blots confirmed that both the brain and midgut of females are likely sources of NPF, found at its highest hemolymph titer before and 24 h after a blood meal.
Keywords: Index terms; Insect; Diptera; Midgut; Peptide hormone; Neuropeptide Y;

A novel GGNG-related neuropeptide from the polychaete Perinereis vancaurica by O Matsushima; H Takahama; Y Ono; T Nagahama; F Morishita; Y Furukawa; E Iwakoshi-Ukena; M Hisada; K Takuwa-Kuroda; H Minakata (1379-1390).
The GGNG peptides are myoactive peptides so far identified from earthworms and leeches, which are the earthworm excitatory peptides (EEP) and the leech excitatory peptide (LEP), respectively. A novel GGNG peptide was isolated and structurally determined from a marine polychaete, Perinereis vancaurica, using a combination of immunological assay and high performance liquid chromatography (HPLC). The peptide was a pentadecapeptide whose amino acid sequence was similar to that of EEP and LEP, and showed myoactivity on isolated esophagus of P. vancaurica with a threshold concentration of 10−10  M. The peptide was designated as polychaete excitatory peptide (PEP). Amidation of the alpha-carboxyl group of C-terminal residue occurred in PEP. This is the case for LEP, but not for EEP. The cDNA cloning revealed that the structure of the PEP precursor is more similar to the EEP precursor than to the LEP precursor. Immunohistochemical staining showed the presence of PEP in several neurons of central nervous system (CNS) as somata and neuropile structure, epithelial cells of the pharynx and epidermal cells throughout the body wall. Altogether these results support the physiological significance of PEP in regulation of the CNS neural activity and the peripheral myoactivity.
Keywords: Polychaete; Annelid; Bioactive peptide; Neuropeptide; Epitheliopeptide; GGNG peptide; Perinereis; cDNA; Immunohistochemistry; Myoactivity; Amidation;

Histatin 5 and derivatives by A.L.A Ruissen; J Groenink; W Van ’t Hof; E Walgreen-Weterings; J van Marle; H.A van Veen; W.F Voorhout; E.C.I Veerman; A.V Nieuw Amerongen (1391-1399).
Histatins, a family of cationic peptides present in saliva, are active against the opportunistic yeast Candida albicans. The mechanism of action is still unclear. Histatin 5 and more potent synthetic variants, dhvar4 and dhvar5, were used to study localization and effects on morphology on the ultra-structural level. Although all peptides induced leakage, no association with the plasma membrane, indicative for permanent pores, was observed with immuno-gold-labeling. Freeze-fracturing showed severe changes of the plasma membrane. Together with, for the dhvars, the loss of intracellular integrity, this suggests that leakage may be a secondary effect rather than an effect of formation of permanent pores.
Keywords: Histatin 5; Dhvar4; Dhvar5; Antimicrobial peptides; Innate immunity; Candida albicans; Saliva;

Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2 by Steven Fried; Kim O’Neill; Brian E Hawes (1401-1408).
Rhesus monkey MCH-R1 and MCH-R2 receptors were cloned. Amino acid homology is 98.8% between monkey and human MCH-R1, while monkey and human MCH-R2 are 98% homologous. Binding and intracellular signaling characteristics of the monkey receptors were compared with the human homologues. The results demonstrate that MCH binds to the monkey MCH-R1 receptor with a K d of 6.5 nM and monkey MCH-R2 with a K d of 2.2 nM similar to K d values for human MCH-R1 and MCH-R2. Additionally, monkey MCH-R1 couples through Gi/Go and Gq-type G proteins similar to human MCH-R1 whereas monkey and human MCH-R2 utilize the Gq signaling pathway.
Keywords: MCH; Receptor; G protein; Rhesus monkey; Intracellular signaling; Amino acid sequence; Nucleic acid sequence;

The regulation of cellular levels of α-melanocyte stimulating factor (α-MSH) and β-endorphin in response to stimulated secretion from intermediate pituitary cells in primary culture was investigated in this study. Regulation of the cell content of α-MSH and β-endorphin occurred in two phases consisting of (a) initial depletion of cellular levels of these peptide hormones during short-term secretion (3 h) induced by isoproterenol, forskolin, or phorbol myristate acetate (PMA) which was followed by (b) long-term (24 h) increases in cellular levels of α-MSH and β-endorphin in response to stimulated secretion induced by isoproterenol and PMA. In short-term experiments (3 h), cellular levels of α-MSH and β-endorphin were reduced by 30–50% during stimulated secretion of these peptide hormones by isoproterenol (agonist for the β-adrenergic receptor), forskolin that activates protein kinase A (PKA), and PMA that activates protein kinase C (PKC). Moreover, dopamine inhibited isoproterenol-induced depletion of cellular α-MSH and β-endorphin. During long-term incubation of cells (24 h) with isoproterenol, cellular α-MSH and β-endorphin were increased to twice that of controls (unstimulated cells). Treatment with PMA for 24 h also increased cellular levels of α-MSH and β-endorphin. Moreover, cellular levels of α-MSH and β-endorphin were decreased during long-term treatment of cells with an aspartyl protease inhibitor, pepstatin A, and with the cysteine protease inhibitor E64c. These results implicate aspartyl and cysteine proteases in the cellular production of α-MSH and β-endorphin that requires proteolytic processing of their common precursor proopiomelanocortin (POMC). These findings demonstrate the parallel regulation of cellular levels of α-MSH and β-endorphin during their cosecretion, which may involve aspartyl and cysteine proteases in the metabolism of these peptide hormones.
Keywords: α-MSH; β-Endorphin; Intermediate pituitary; Peptide hormone secretion; Regulation of cellular α-MSH and β-endorphin; Peptide hormone biosynthesis;

Noncompetitive nature of oxytocin antagonists with general structure Mpa1Xxx2Sar7Arg8 by J. Havass; K. Bakos; Á. Márki; R. Gáspár; L. Gera; J.M. Stewart; F. Fülöp; G.K. Tóth; I. Zupkó; G. Falkay (1419-1425).
Eight oxytocin (OT) antagonists with general structure Mpa1Sar7Arg8, substituted at position 2 with conformationally constrained and bulky amino acids, were synthesized and pharmacologically tested. Binding affinities and selectivities of compounds for OT, and vasopressin receptor subtypes were investigated. In vitro effects of antagonists were evaluated via inhibition of OT-induced contractions of isolated guinea-pig uterus. The abilities of OT antagonists to inhibit spontaneous contractility in 24 h postpartum rat uterus were investigated. These peptides exhibited pseudoirreversible pharmacological properties, and comprise a novel group of OT antagonists for potential clinical use. Their noncompetitive pharmacological nature can be of therapeutic benefit through a sustained effect on myometrium.
Keywords: Oxytocin antagonist; Noncompetitive; Tocolysis;

The ability of sodium deficiency to stimulate vasopressin (VP) release was examined by determining if sodium deficiency sensitizes the animal to the behavioral disruption caused by intraventricular injections of VP. In sodium-replete rats, intraventricular injections of 50 ng VP on Day 1 had no effect on behavior, but this dose elicited abnormal behaviors (barrel rolls, hind-limb extensions) when administered on Day 2, indicating a sensitization phenomenon. In separate experiments, the first intraventricular injection of 50 ng VP in sodium-deficient but not in sodium-replete rats also elicited barrel rotations followed by hind-limb extension. Intraventricular injection of VP also disrupted motor behavior in sodium-replete rats that had multiple prior experiences with sodium deficiency but not in naive rats. These results show that sodium deficiency can mimic the effect of central injections of VP in sensitizing the brain to the behavioral effects of exogenous VP. This suggests that sodium deficiency induces the central release of VP.
Keywords: Neuropeptides; Convulsions; Sensitization; Neurohypophyseal; Salt appetite;

Interactions of human secretin with sterically stabilized phospholipid micelles amplify peptide-induced vasodilation in vivo by Salil Gandhi; Takaya Tsueshita; Hayat Önyüksel; Rinku Chandiwala; Israel Rubinstein (1433-1439).
Secretin, a 27-amino acid neuropeptide, is a member of the glucagon/secretin/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides that elicits transient vasodilation in vivo. The purpose of this study was to determine whether association of human secretin with sterically stabilized phospholipid micelles (SSM) amplifies the vasorelaxant effects of the peptide in the peripheral microcirculation in vivo. We found that secretin in saline evoked significant concentration-dependent vasodilation in the intact hamster cheek pouch microcirculation (P<0.05). This response was potentiated and prolonged significantly when secretin was associated with SSM (P<0.05). Vasodilation evoked by secretin in saline and secretin in SSM was abrogated by VIP10–28, a VIP receptor antagonist, but not by PACAP6–38, a PACAP receptor antagonist, or Hoe140, a selective bradykinin B2 receptor antagonist. Collectively, these data indicate that self-association of human secretin with SSM significantly amplifies peptide vasoreactivity in the intact peripheral microcirculation through activation of VIP receptors. We suggest that the vasoactive effects of human secretin in vivo are, in part, phospholipid-dependent.
Keywords: Microcirculation; Micelles; Neuropeptide; Vasomotor tone; Receptor antagonist; VIP; DSPE-PEG2000;

Cardiotrophin-1 stimulates endothelin-1 via gp130 in vascular endothelial cells by Michihisa Jougasaki; Amy M Larsen; Alessandro Cataliotti; David C Christiansen; John C Burnett (1441-1447).
Endothelin-1 (ET-1) is a vasoconstricting and mitogenic peptide released from vascular endothelial cells under normal and pathophysiological conditions, and synthesis and secretion of ET-1 are stimulated by cytokines. Cardiotrophin-1 (CT-1) is a new member of the interleukin-6-type cytokines that induce biological actions through the glycoprotein (gp) 130. The present study was designed to determine the presence of CT-1 and the gp130 cytokine system in vascular endothelial cells and to investigate whether CT-1 stimulates synthesis and secretion of ET-1 in the vascular endothelial cells. We first sought to determine gene expression and immunoreactivity of CT-1, gp130 and ET-1 in cultured canine aortic endothelial cells (CAECs) using Northern blot analysis and immunocytochemistry, which revealed the presence of CT-1 and gp130 together with ET-1 in CAECs. CT-1 increased ET-1 gene expression in CAECs, and stimulated ET-1 secretion from CAECs in a dose-dependent manner. Furthermore, inhibition of gp130 by monoclonal antibody attenuated ET-1 secretion from CAECs, suggesting that actions of CT-1 on the secretion of ET-1 are mediated through gp130 receptor system. The present study, therefore, reports the presence of CT-1 and gp130 in vascular endothelial cells and mechanisms of secretion of ET-1 related to this cytokine system.
Keywords: Endothelium; Hormone; Immunocytochemistry; Peptides; Radioimmunoassay;

Angiotensin-(1–7) and bradykinin interaction in diabetes mellitus: in vivo study by Maria A Oliveira; Maria Helena C Carvalho; Dorothy Nigro; Rita de Cássia A.T Passaglia; Zuleica B Fortes (1449-1455).
The interaction between angiotensin-(1–7) (Ang-(1–7)) and bradykinin (BK) was determined in the mesentery of anesthetized Wistar alloxan-diabetic and non-diabetic rats using intravital microscopy. Impaired BK vasodilation observed in arterioles of diabetic rats was restored by acute and chronic insulin treatment as well as by enalapril. Though capable of potentiating BK in non-diabetic rats, Ang-(1–7) did not potentiate BK in diabetic rats. Chronic but not acute insulin treatment restored the potentiation, whereas enalapril did not. Potassium channel blockade (by tetraethylammonium (TEA)) but not nitric oxide (NO) synthase inhibition (by N-ϖ-nitro-l-arginine-methyl-esther (l-NAME)) abolished the restorative effect of insulin. Our data allow us to suggest that the alteration observed is restored by insulin by a mechanism involving membrane hyperpolarization but not NO release. The beneficial effect of enalapril in diabetes might not involve the potentiation of BK by Ang-(1–7).
Keywords: Bradykinin; Angiotensin-(1–7); Diabetes mellitus; Membrane hyperpolarization; Microcirculation;

Interaction of linear and cyclic peptide antagonists at the human B2 kinin receptor by Paola Cucchi; Stefania Meini; Laura Quartara; Alessandro Giolitti; Sabrina Zappitelli; Luigi Rotondaro; Carlo Alberto Maggi (1457-1463).
The ligand receptor interactions involving the C-terminal moiety of kinin B2 receptor antagonists Icatibant (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-Dtic-Oic-Arg-OH), MEN 11270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-Dtic-Oic-Arg)c(7γ-10α)) and a series of analogs modified in position 10 were investigated by radioligand-binding experiments at the wild type (WT) and at the Ser111Ala and Ser111Lys mutant human kinin B2 receptors. Icatibant and [Lys10]-Icatibant maintained the same high affinity towards the three receptors. For Icatibant-NH2, [Ala10]-Icatibant, MEN 11270 and [Glu10]-MEN 11270, the changes in affinity at the WT and Ser111Lys receptors indicated that the presence of a net positive or negative charge at the C-terminal moiety of these peptides caused a decrease in affinity to the WT receptor and that Ser111 residue is in proximity of the side chain of residue 10. The changes in affinity measured with [desArg10]-Icatibant and [desArg10]-Icatibant-NH2, moreover, confirmed that a C-terminal charge compensation between the positive charge of Arg10 side chain and the C-terminal free carboxylic function favours a high affinity interaction.
Keywords: Bradykinin; Bradykinin B2 receptor; Bradykinin antagonists; Icatibant; MEN 11270;

Comparative effects of angiotensin IV and two hemorphins on angiotensin-converting enzyme activity by Ingrid Fruitier-Arnaudin; Marie Cohen; Stéphanie Bordenave; Frédéric Sannier; Jean-Marie Piot (1465-1470).
The role of angiotensin IV (AngIV) in the regulation of angiotensin-converting enzyme (ACE) was studied in vitro. This study demonstrates that this active fragment appeared as a novel endogenous ACE inhibitor. Inhibitory kinetic studies revealed that AngIV acts as a purely competitive inhibitor with a K i value of 35 μM. AngIV was found to be quite resistant to ACE hydrolysis opposite to hemorphins which are both ACE inhibitors and substrates. In order to confirm a putative role of AngIV and hemorphins in the Renin–Angiotensin system (RAS) regulation, we studied their influence on AngI conversion. We noticed that 16.7 μM of both peptides decreased more than 50% of AngI conversion to AngII in vitro. The capacity of hemorphins, particularly LVVH-7, and AngIV to inhibit ACE activity here suggests a synergistic relation between these two peptides and the regulation of RAS.
Keywords: Endogenous ACE activity regulation; Angiotensin IV; Hemorphins;

The neuropeptide PACAP attenuates β-amyloid (1–42)-induced toxicity in PC12 cells by Satomi Onoue; Kosuke Endo; Keiichi Ohshima; Takehiko Yajima; Kazuhisa Kashimoto (1471-1478).
Pituitary adenylate cyclase activating polypeptide (PACAP) modulates neurotransmission in the central and peripheral nervous systems. In vitro and in vivo studies have shown the protective effects of PACAP against neuronal damage induced by ischemia and agonists of NMDA-type glutamate receptors. Here, we demonstrated that PACAP also protected against neuronal toxicity induced by β-amyloid (Aβ) peptide, aggregation of which is a causative factor for Alzheimer’s disease. PACAP (10−9  M) rescued 80% of decreased cell viability and 50% of elevated caspase-3 activity that resulted from exposure of PC12 cells to Aβ. PACAP was at least 104-fold more effective than other neuropeptides including vasoactive intestinal peptide (VIP) and humanin, which correlated with the level of cAMP accumulation. Thus, our results suggested that PACAP attenuates Aβ-induced cell death in PC12 cells through an increase in cAMP and that caspase-3 deactivation by PACAP is involved in the signaling pathway for this neuroprotection.
Keywords: PACAP; VIP; Neuropeptides; cAMP; Humanin; PC12 cells; β-Amyloid; Alzheimer’s disease; Neuroprotection;

Co-localization of hypocretin-1 and hypocretin-2 in the cat hypothalamus and brainstem by Jian-Hua Zhang; Sharon Sampogna; Francisco R Morales; Michael H Chase (1479-1483).
Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) are two recently discovered hypothalamic neuropeptides. In the present study, using double immunofluorescent techniques, the co-localization of hcrt-1 and hcrt-2 was examined in neuronal soma and fibers/terminals located, respectively, in the cat hypothalamus and brainstem. In the hypothalamus, all hcrt-1 positive neuronal soma also displayed hcrt-2 immunoreactivity. In the brainstem, both hcrt-1 and hcrt-2 antibodies labeled the same fibers/terminals, indicating that hcrt-1 and hcrt-2 co-localize not only in the neuronal soma (hypothalamus) but also in their fibers/terminals (brainstem). If both peptides are released following neuronal activity, then the distinct effects of these peptides in the brain are likely to depend on the types of postsynaptic receptors that are activated.
Keywords: Hypocretin; Immunofluorescence; Hypothalamus; Brainstem; Cat;

The actions of neuropeptide Y (NPY) are mediated by at least six G-protein coupled receptors denoted as Y1, Y2, Y3, Y4, Y5, and y6. Investigations using receptor selective ligands and receptor knock-out mice suggest that NPY effects on feeding are mediated by both Y1 and Y5 receptors. We have previously shown that Cys-dimers of NPY C-terminal peptides exhibit Y1 selectivity relative to Y2 receptors. Re-investigation of their selectivity with respect to the newly cloned receptors, has identified bis(31/31′) {[Cys31, Nva34]NPY(27–36)-NH2} (BWX-46) as a Y5 receptor selective agonist. BWX-46 selectively bound Y5 receptors, and inhibited cAMP synthesis by Y5 cells with potencies comparable to that of NPY. Moreover, BWX-46 (10 μM) exhibited no significant effect on the cAMP synthesis by Y1, Y2, and Y4 cells. Thus, BWX-46 constitutes the lowest molecular weight Y5 selective agonist reported to date. Intrahypothalamic (iht)-injection of 30 and 40 μg of BWX-46 stimulated the food intake by rats in a gradual manner, reaching maximal level 8 h after injection. This response was similar to that exhibited by other Y5 selective agonists, but differed from that of NPY, which exhibited a rapid orexigenic stimulus within 1 h. It is suggested that the differences in the orexigenic stimuli of NPY and Y5 agonists may be due to their differences in the signal transduction mechanisms.
Keywords: Agonist; CREB; Feeding; ICER; cAMP; NPY; Y1 receptor; Y5 receptor;

Plasma glucagon-like peptide-1 (GLP-1) responses to duodenal fat and glucose infusions in lean and obese men by Christine Feinle; Ian M Chapman; Judith Wishart; Michael Horowitz (1491-1495).
It has been suggested that obesity is associated with a reduced glucagon-like peptide-1 (GLP-1) response to oral carbohydrate, but not fat. The latter may, however, be attributable to changes in gastric emptying. We have assessed plasma GLP-1 levels in response to these infusions in lean and obese subjects. Seven healthy lean (body mass index (BMI), 19.1–24.6 kg/m2) and seven obese (BMI, 31.3–40.8 kg/m2) young men received an intraduodenal infusion of glucose and fat for 120 min (2.86 kcal/min) on two separate days. Blood samples for plasma GLP-1 were obtained at baseline and every 20 min during the infusion. Plasma GLP-1 increased during infusion of glucose and fat (P=0.001), but there were no differences between lean and obese subjects, nor the two nutrients. We conclude that GLP-1 secretion in response to duodenal infusion of glucose and fat is not altered in obese subjects.
Keywords: Glucagon-like peptide-1; Obesity; Glucose; Fat; Duodenal infusion;

Alterations in GHRH binding and GHRH receptor mRNA in the pituitary of adult dw/dw rats by János Gardi; Robert C Speth; Ping Taishi; Bálint Kacsóh; Ferenc Obál; James M Krueger (1497-1502).
Lewis dwarf (dw/dw) rats exhibit growth hormone (GH) deficiency and growth retardation linked to a malfunction of GHRH signaling. In this study, GHRH-receptor (GHRH-R) binding and mRNA in the pituitary of adult male dw/dw and age-matched normal Lewis rats was measured by radioligand binding assay and real-time PCR. Only one of nine pools of dw/dw pituitary membranes revealed detectable binding of [His1, 125 I -Tyr10, Nle27]hGHRH(1–32) amide (B max; 4.3 fmol/mg protein). In contrast, GHRH-R binding was 22.4±2.60 fmol/mg protein in normal Lewis rats. mRNA for GHRH-R was detectable in all dw/dw rat pituitaries examined, averaging 21% that of Lewis rats. Low expression of GHRH-R reflects reduced GHRH-R mRNA as well as a possible reduction in translation of the receptor protein.
Keywords: Dwarf; Rat; Growth hormone-releasing hormone; Receptor; Binding; mRNA; Anterior pituitary; Somatotroph;

The cyclic somatostatin (SST) analogue, cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]) (cSSTA), has been widely used as somatostatin antagonist. In the human neuroblastoma cell line SH-SY5Y the cyclopeptide acts as a somatostatin receptor agonist. Similar to SST, cSSTA inhibits cell proliferation, activates the protein tyrosine phosphatase SHP-2, and stimulates the activity of mitogen-activated protein kinase. These results suggest that in SH-SY5Y neuroblastoma cells somatostatin receptors may exist which exhibit altered antagonist binding properties.
Keywords: Somatostatin antagonist; Cell growth inhibition; Protein tyrosine phosphatase; MAP kinase;

G protein-dependent activation of mast cell by peptides and basic secretagogues by Xavier Ferry; Stephan Brehin; Rehab Kamel; Yves Landry (1507-1515).
Signaling pathways leading to exocytosis and arachidonate release from serosal mast cells by basic secretagogues, including cationic peptides, arise from the involvement of βγ subunits from Gi2 and Gi3 GTP-binding proteins. The original concept that basic secretagogues directly interact with G proteins implicated the entry of secretagogues into mast cells. This has been demonstrated only for the neuropeptide substance P. Basic secretagogues might share a common mechanism of penetration with the newly described cell-penetrating peptides. The involvement of some membrane transporter or non-selective membrane receptor to basic secretagogues cannot be excluded.
Keywords: Basic secretagogues; Mast cells; G proteins; Cell-penetrating peptides; Neuropeptides; Venom peptides; Defensins; Compound 48/80; Mastoparan;

Interaction of xenin with the neurotensin receptor of guinea pig enteral smooth muscles by Gerhard E Feurle; Jörg W Metzger; Alexandra Grudinki; Gerd Hamscher (1519-1525).
Xenin, a 25 amino acid peptide, interacts with the neurotensin receptor subtype 1 of intestinal muscles of the guinea pig. Replacement of the C-terminal Lys–Arg peptide bond in xenin 6 by a reduced pseudo-peptide bond augmented binding affinity to isolated jejunal and colonic muscle membranes by factors of 7.7 and 21.0 respectively; the potency to contract the jejunum and to relax the colon was increased by factors of 3.2 and 1.3. The C-terminus Trp-Ile-Leu (WIL) of xenin, in contrast to the C-terminus Tyr-Ile-Leu (YIL) of neurotensin, bound competitively to the muscle membranes. WIL blocked the contractile action of xenin in the jejunum and was synergistic with the relaxing action in the colon. The Lys–Arg motif and Trp in the C-terminus of xenin are essential structures in the action of xenin on the enteral smooth muscle receptors.
Keywords: Xenin; Neurotensin; Neurotensin receptor; Smooth muscle; Guinea pig; Intestine; Reduced ψ pseudo-peptide bond;