Peptides (v.24, #5)
IFC(editorial board) (IFC).
A retroviral-derived peptide phosphorylates protein kinase D/protein kinase Cμ involving phospholipase C and protein kinase C by Voravich Luangwedchakarn; Noorbibi K. Day; Remi Hitchcock; Pam G. Brown; Danica L. Lerner; Rajivi P. Rucker; George J. Cianciolo; Robert A. Good; Soichi Haraguchi (631-637).
CKS-17, a synthetic peptide representing a unique amino acid motif which is highly conserved in retroviral transmembrane proteins and other immunoregulatory proteins, induces selective immunomodulatory functions, both in vitro and in vivo, and activates intracellular signaling molecules such as cAMP and extracellular signal-regulated kinases. In the present study, using Jurkat T-cells, we report that CKS-17 phosphorylates protein kinase D (PKD)/protein kinase C (PKC) μ. Total cell extracts from CKS-17-stimulated Jurkat cells were immunoblotted with an anti-phospho-PKCμ antibody. The results show that CKS-17 significantly phosphorylates PKD/PKCμ in a dose- and time-dependent manner. Treatment of cells with the PKC inhibitors GF 109203X and Ro 31-8220, which do not act directly on PKD/PKCμ, attenuates CKS-17-induced phosphorylation of PKD/PKCμ. In contrast, the selective protein kinase A inhibitor H-89 does not reverse the action of CKS-17. Furthermore, a phospholipase C (PLC) selective inhibitor, U-73122, completely blocks the phosphorylation of PKD/PKCμ by CKS-17 while a negative control U-73343 does not. In addition, substitution of lysine for arginine residues in the CKS-17 sequence completely abrogates the ability of CKS-17 to phosphorylate PKD/PKCμ. These results clearly indicate that CKS-17 phosphorylates PKD/PKCμ through a PLC- and PKC-dependent mechanism and that arginine residues play an essential role in this activity of CKS-17, presenting a novel modality of the retroviral peptide CKS-17 and molecular interaction of this compound with target cells.
Keywords: CKS-17; Synthetic peptide; Retroviral transmembrane protein; Signal transduction; Protein kinase D; Protein kinase Cμ; Jurkat T-cell line; Human;
Purification and characterization of a ubiquitin-like peptide with macrophage stimulating, antiproliferative and ribonuclease activities from the mushroom Agrocybe cylindracea by Patrick H.K. Ngai; H.X. Wang; T.B. Ng (639-645).
A peptide, with a molecular mass of 9.5 kDa and demonstrating an N-terminal sequence similar to ubiquitin, was isolated from fruiting bodies of the mushroom Agrocybe cylindracea. The peptide was isolated with a purification protocol involving ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, FPLC-ion exchange chromatography on Mono S and FPLC-gel filtration on Superdex 75. The peptide was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and Mono S. It showed antiproliferative activity on leukemia cell line (M1) and hepatoma cell line (HepG2), and enhanced nitric oxide production in murine peritoneal macrophages with a potency comparable to that of lipopolysaccharide. A pH of 6.0 was required for optimal RNase activity. Its RNase activity was stable over the temperature range of 0–60 °C. It exerted ribonucleolytic activity preferentially on polyC, much lower activity on polyU, and negligible activity on polyA and polyG.
Keywords: Agrocybe cylindracea; Ubiquitin; Mushroom;
Peptides of the liver stage antigen-1 (LSA-1) of Plasmodium falciparum bind to human hepatocytes by Javier E. Garcı́a; Alvaro Puentes; Ramsés López; Ricardo Vera; Jorge Suárez; Luis Rodrı́guez; Hernando Curtidor; Marisol Ocampo; Diana Tovar; Martha Forero; Adriana Bermudez; Jimena Cortés; Mauricio Urquiza; Manuel E. Patarroyo (647-657).
Synthetic peptides from the liver stage antigen-1 (LSA-1) antigen sequence were used in HepG2 cell and erythrocyte binding assays to identify regions that could be involved in parasite invasion. LSA-1 protein peptides 20630 ( 21 INGKIIKNSEKDEIIKSNLRY 40 ), 20637 ( 157 KEKLQGQQSDSEQERRAY 173 ), 20638 ( 174 KEKLQEQQSDLEQERLAY 190 ) and 20639 ( 191 KEKLQEQQSDLEQERRAY 207 ) had high binding activity in HepG2 assays. Were located in immunogenic regions; peptide cell binding was saturable. Peptide 20630 bound specifically to 48 kDa HepG2 membrane surface protein. LSA-1 peptides 20630 ( 21 INGKIIKNSEKDEIIKSNLRY 40 ) and 20633 ( 81 DKELTMSNVKNVSQTNFKSLY 100 ) showed specific erythrocyte binding activity and inhibited merozoite invasion of erythrocytes in vitro. A monkey serum prepared against LSA-1 20630 peptide analog (CGINGKNIKNAEKPMIIKSNLRGC) inhibited merozoite invasion in vitro. The data suggest LSA-1 “High Activity Binding Peptides” could play a possible role in hepatic cell invasion as well as merozoite invasion of erythrocytes.
Keywords: P. falciparum; Critical residues; Liver stage antigen (LSA); High activity binding peptides (HABPs); Phosphate buffered saline (PBS); Red blood cells (RBC);
Cicerarin, a novel antifungal peptide from the green chickpea by K.T. Chu; K.H. Liu; T.B. Ng (659-663).
A peptide designated cicerarin, with an N-terminal amino acid sequence VKSTGRADDDLAVKTKYLPP dissimilar from known proteins and peptides and a molecular mass of 8 kDa, was isolated from seeds of the green chickpea Cicer arietinum cv green chickpea. Cicerarin was isolated with a procedure that involved ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, and gel filtration by fast protein liquid chromatography on Superdex 75. Cicerarin was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel in 10 mM Tris–HCl buffer (pH 7.3). Cicerarin exerted antifungal activity against Botrytis cinerea, Mycosphaerella arachidicola, and Physalospora piricola. The antifungal activity was preserved after exposure to 100 °C for 15 min.
Keywords: Cicerarin; Green chickpea; Antifungal;
Prediction of β-turns with learning machines by Yu-Dong Cai; Xiao-Jun Liu; Yi-Xue Li; Xue-biao Xu; Kuo-Chen Chou (665-669).
The support vector machine approach was introduced to predict the β-turns in proteins. The overall self-consistency rate by the re-substitution test for the training or learning dataset reached 100%. Both the training dataset and independent testing dataset were taken from Chou [J. Pept. Res. 49 (1997) 120]. The success prediction rates by the jackknife test for the β-turn subset of 455 tetrapeptides and non-β-turn subset of 3807 tetrapeptides in the training dataset were 58.1 and 98.4%, respectively. The success rates with the independent dataset test for the β-turn subset of 110 tetrapeptides and non-β-turn subset of 30,231 tetrapeptides were 69.1 and 97.3%, respectively. The results obtained from this study support the conclusion that the residue-coupled effect along a tetrapeptide is important for the formation of a β-turn.
Keywords: Jackknife test; Dataset; Tetrapeptides;
Hypophysotropic activity of histone H3 in vitro by Oscar A. Brown; Yolanda E. Sosa; Diana Naumovich; Claudia B. Hereñú; Rodolfo G. Goya (671-678).
To assess the effect of histone H3 on pituitary hormone secretion, rat anterior pituitary (AP) cells were used and growth hormone, prolactin, thyrotropin, luteinizing hormone and follicle stimulating hormone measured by radioimmunoassay. Incubation of cells with H3 (1, 6, and 30 μM) stimulated the release of all five hormones in a dose-dependent manner. This effect was blocked by preincubation of H3 with an anti-H3 antibody. Incubation of AP cells with 6 μM H3 in the presence of specific AP hormone secretagogues (GRP-6, thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH)) showed additive effects on hormone secretion. Pharmacological experiments suggested that calcium- and diacylglycerol- (DAG) associated pathways, but not cAMP, participate in the hypophysiotropic activity of H3. Our results confirm previous evidence that histones may act as hypophysiotropic signals.
Keywords: Histones; Hypophysotropic activity; Pituitary cells; Second messengers; Apoptotic signals;
Humanin peptides block calcium influx of rat hippocampal neurons by altering fibrogenesis of Aβ1–40 by Ping Zou; Yanan Ding; Yinlin Sha; Baihe Hu; Songqing Nie (679-685).
Humanin peptides (including HN, HNG and other mutants) were reported previously that antagonize neurotoxicity caused by various familial Alzheimer’s disease (FAD) genes and Aβ derivatives. Herein, we describe the aggregation dynamics and the representative morphological characteristics of Aβ1–40 after different time of addition humanin peptides, which revealed that (a) the interactions of both HN and HNG with Aβ1–40 induced quick and significant increase of light-scattering intensity, and (b) HNG also caused obvious morphological alteration from fibrillary to amorphous. In the meantime, the experiments also revealed that the interaction of HNG with Aβ1–40 could decrease Aβ1–40-induced calcium rise, an initial event accompanying Aβ1–40-induced apoptosis of cultured neurons. Our results indicate that HNG can protect neurons by altering Aβ1–40 morphology.
Keywords: Humanin; Electron microscopy; Aβ aggregation; Calcium influx; Neurotoxicity;
Co-existence of leptin- and orexin-receptors in feeding-regulating neurons in the hypothalamic arcuate nucleus—a triple labeling study by Hisayuki Funahashi; Shuori Yamada; Haruaki Kageyama; Fumiko Takenoya; Jian-Lian Guan; Seiji Shioda (687-694).
The arcuate nucleus (ARC) of the hypothalamus has been identified as a prime feeding regulating center in the brain. Several feeding regulating peptides, such as neuropeptide Y (NPY) and proopiomelanocortin (POMC), are present in neurons of the ARC, which also serves as a primary targeting site for leptin, a feeding inhibiting hormone secreted predominantly by adipose tissues, and for orexin (OX)-containing neurons. OX is expressed exclusively around the lateral hypothalamus, an area also established as a feeding regulating center. Some recent physiological analyses have shown that NPY- and POMC-containing neurons are activated or inactivated by leptin and OX. Moreover, we have already shown, using double immunohistochemical staining techniques, that NPY- and POMC-containing neurons express leptin receptors (LR) and orexin type 1 receptors (OX-1R). However, no morphological study has yet described the possibility of whether or not these arcuate neurons are influenced by both leptin and OX simultaneously. In order to address this issue, we performed histochemistry on ARC neurons using a triple immunofluorescence method. We found that 77 out of 213 NPY- and 99 out of 165 POMC-immunoreactive neurons co-localized with both LR- and OX-1R-immunoreactivities. These findings strongly suggest that both NPY- and POMC-containing neurons are regulated simultaneously by both leptin and OX.
Keywords: Leptin; Orexin; Arcuate nucleus;
Leukocyte motility in response to neuropeptides is heparan sulfate proteoglycan dependent by Nicole C. Kaneider; Petra Egger; Angela M. Djanani; Christian J. Wiedermann (695-700).
Activation of neuropeptide receptors on leukocytes induces chemotaxis. We determined in Boyden chambers with micropore filters, whether in human monocytes and lymphocytes this migratory response is heparan sulfate proteoglycan (HSPG) dependent. Chemotaxis toward calcitonin gene-related peptide, secretoneurin, vasoactive intestinal peptide (VIP), and substance P (SP) was abolished by removal of heparan sulfate side chains from cell surface proteoglycans or by addition of anti-syndecan-4 antibodies. Inhibition of neuropeptide-induced chemotaxis by dimethyl sphingosine (DMS), an inhibitor of sphingosine kinase, indicates transactivation of the sphingosine-1-phosphate chemotaxis pathway which was previously identified as being syndecan-4-related. Data suggest that HSPGs are involved in neuropeptide-induced chemotaxis of leukocytes.
Keywords: Chemotaxis; Monocyte; Lymphocyte; Glycosaminoglycans; Chemokines; Neuropeptides; Signaling;
Effects of α-melanotropin C-terminal tripeptide analogues on macrophage NO production by Ruta Muceniece; Liga Krigere; Helga Süli-Vargha; Jarl E.S. Wikberg (701-707).
The C-terminal tripeptide of melanocyte-stimulating hormone, MSH (11–13) (Lys-Pro-Val), possesses strong anti-inflammatory actions, which are mediated via mechanisms that are not fully understood. To shed more light into these mechanisms we have here synthesised and evaluated the activities of l- and d-Val substituted cyclic modifications of MSH (11–13) on nitric oxide (NO) in macrophage RAW 264.7 cells, as well as on binding to melanocortin receptors (MCRs) in B16-F1 and MCR expressing insect cells, and for effects on cAMP. MSH (11–13) and its analogues did neither bind to MCRs nor stimulate cAMP in RAW 264.7 and B16-F1 cells, except H-▪, which showed a tendency to increase cAMP at high (10–100 μM) concentrations. However, all investigated peptides dose dependently inhibited NO in LPS/IFN-γ-stimulated RAW 264.7, cells with a structure activity relationship suggesting the existence of a distinct receptive site. This site appears to be distinct from the MCRs and not linked with cAMP.
Keywords: Melanocortin receptors; Binding; cAMP generation; NO production; MSH (11–13) analogues;
Regulation of TNF-α secretion by a specific melanocortin-1 receptor peptide agonist by Diane M. Ignar; John L. Andrews; Marilyn Jansen; Michelle M. Eilert; Heather M. Pink; Peiyuan Lin; Ronald G. Sherrill; Jerzy R. Szewczyk; James G. Conway (709-716).
The lack of specific pharmacological tools has impeded the evaluation of the role of each melanocortin receptor (MCR) subtype in the myriad physiological effects of melanocortins. 154N-5 is an octapeptide (MFRdWFKPV-NH2) that was first identified as an MC1R antagonist in Xenopus melanophores [J. Biol. Chem. 269 (1994) 29846]. In this manuscript, we show that 154N-5 is a specific agonist for human and murine MC1R. The peptide has negligible activity at MC3R and MC4R and is 25-fold less potent and a weak agonist at MC5R. 154N-5 was tested in both a cellular and an animal model of tumor necrosis factor-α (TNF-α) secretion. The inhibitory efficacy of 154N-5 on TNF-α secretion in both models was similar to the nonselective agonist NDP-α-melanocyte stimulating hormone (NDP-αMSH), thus, we conclude that inhibition of TNF-α secretion by melanocortin peptides is mediated by MC1R. 154N-5 is a valuable new tool for the evaluation of specific contribution of MC1R agonism to physiological and pathological processes.
Keywords: Melanocortin; TNF-α; α-MSH; Melanocortin-1;
Regulation of ACTH levels in anterior pituitary cells during stimulated secretion: evidence for aspartyl and cysteine proteases in the cellular metabolism of ACTH by Catherine Sei; Thomas Toneff; Wade Aaron; Vivian Y.H. Hook (717-725).
The regulation of cellular levels of adrenocorticotropin hormone (ACTH) in response to stimulated secretion was investigated to define the extent of cellular depletion of ACTH and subsequent increases to replenish ACTH levels in anterior pituitary cells (in primary culture). Treatment of cells with secretagogues for short-term incubation times (hours) resulted in extensive depletion of cellular ACTH. Corticotropin releasing factor (CRF) induced depletion of cellular levels of ACTH by 60–70% of control levels. The CRF-induced reduction of cellular ACTH was inhibited by the glucocorticoid dexamethasone. Phorbol myristate acetate (PMA), which stimulates protein kinase C (PKC), reduced ACTH levels by 50–60%. Forskolin, a stimulator of cAMP production, produced a moderate reduction in cellular ACTH. During prolonged incubation of cells (2 days) with these secretagogues, further reduction of ACTH levels by 70–80% was observed. However, increased cellular levels of ACTH occurred with continued treatment of cells with secretagogues, which provided nearly complete replenishment of cellular ACTH after 5 days treatment with secretagogues. Notably, the rising levels of cellular ACTH were inhibited by the aspartyl protease inhibitor acetyl-pepstatin A, and by the cysteine protease inhibitor E64d. These results demonstrate that depletion and recovery of ACTH levels are coordinately regulated, and that the increases in cellular levels of ACTH during the recovery phase involves participation of aspartyl and cysteine proteases. Thus, aspartyl and cysteine proteases may be involved in the cellular metabolism of ACTH.
Keywords: ACTH depletion; Secretion; Biosynthesis; Proteases;
Stimulation of rat pancreatic exocrine secretion by urocortin and corticotropin releasing factor by Eduardo A Guzman; Weizhen Zhang; Theodore R Lin; Michael W Mulholland (727-734).
Neural and hormonal mechanisms control pancreatic secretion. The effects of the corticotropin releasing factor (CRF) related neuropeptide urocortin (UCN) on pancreatic exocrine secretion were examined. In anesthetized male rats, pancreatic secretion volume and total protein were assayed. UCN increased pancreatic secretory volume and protein secretion and potentiated cholecytokinin-stimulated protein secretion. Astressin, a non-specific CRF receptor antagonist, inhibited UCN-stimulated protein output while CRF2 receptor antagonist, antisauvagine-30, was without effect. Atropine, but not subdiaphragmatic vagotomy, inhibited UCN-mediated secretion. In acinar cells, UCN did not stimulate release of amylase nor intracellular cAMP. UCN is a pancreatic exocrine secreatagogue with effects mediated through cholinergic intrapancreatic neurons.
Keywords: Pancreatic neurotransmission; Vagotomy; CRF receptor; cAMP;
Anti-analgesic activity of enterostatin (VPDPR) is mediated by corticosterone by Y. Takenaka; F. Nakamura; H. Usui; A.W. Lipkowski; G. Toth; M. Yoshikawa (735-739).
Although enterostatin (VPDPR) inhibited morphine-induced analgesia, it had no affinity for μ-opioid receptors. VPDPR administration was reported to elevate serum corticosterone levels. We found that corticosterone exhibited a similar anti-analgesic effect selective for μ-opioid. Furthermore, the anti-analgesic effect of VPDPR was inhibited by RU486, an antagonist for the glucocorticoid receptor. The anti-analgesic effect of VPDPR was not observed in adrenalectomized mice. These results suggest that the anti-analgesic activity of VPDPR is mediated by corticosterone released from the adrenal cortex.
Keywords: Enterostratin; Anti-analgesic effect; Corticosterone; Adrenalectomy; RU486; μ-Opioid;
Endomorphin-1, an endogenous μ-opioid receptor agonist, improves apomorphine-induced impairment of prepulse inhibition in mice by Makoto Ukai; Ami Okuda (741-744).
The present study was designed to examine the effects of the endogenous μ-opioid receptor agonist endomorphin-1 on prepulse inhibition (PPI) in mice. Although apomorphine (1 mg/kg) produced a marked decrease in PPI, endomorphin-1 (17.5 μg) had no marked effects on PPI or startle amplitude in normal mice. Endomorphin-1 (17.5 μg) inhibited the apomorphine (1 mg/kg)-induced decrease in PPI. β-Funaltrexamine (5 μg), a μ-opioid receptor antagonist, did not significantly antagonize the effects of endomorphin-1 (17.5 μg). Naloxonazine (35 mg/kg), a μ1-opioid receptor antagonist, antagonized the effects of endomorphin-1 (17.5 μg) on the apomorphine (1 mg/kg)-induced decrease in PPI, whereas naloxonazine (35 mg/kg) itself was without significant effects on the apomorphine (1 mg/kg)-induced decrease. These results suggest that endomorphin-1 alleviates the impairment of PPI resulting from the hyperactivity of dopaminergic neurotransmission through the mediation of μ1-opioid receptors.
Keywords: Prepulse inhibition; Endomorphin-1; Opioid receptor; β-Funaltrexamine; Naloxonazine; Apomorphine; Mouse;
Cardiovascular responses to central administration of mu and kappa opioid receptor agonist and antagonist in normal rats by Sumangala P. Rao; Alexandria Conley; Joseph C. Dunbar (745-754).
The response to centrally administered β-endorphin has been characterized by decreasing sympathetic nervous activity and decreased cardiovascular tone. We investigated the effect of the central administration of both mu and kappa opioid receptor agonist and antagonists on cardiovascular responses. The administration of the mu agonist, DAMGO (0.2 nmol) increased the mean arterial pressure (MAP) and stimulated iliac vasoconstriction while higher doses (2 and 20 nmol) decreased MAP and stimulated iliac vasodilation. The administration of the kappa receptor agonist, Dynorphin decreased the MAP and stimulated superior mesenteric vasodilation. β-Funaltrexamine reduced MAP and superior mesenteric vasodilation while nor-binaltorphimine increased MAP and iliac and superior mesenteric vasoconstriction. We conclude that mu receptor activation decrease or increase MAP depending on the mu agonist concentration. However, kappa receptor activation is consistently associated with a decrease in MAP.
Keywords: Opioid receptors; Mu receptors; Kappa receptors; Blood pressure; Vascular flow;
Angiotensinase activities in the kidney of renovascular hypertensive rats by Isabel Prieto; Francisco Hermoso; Marc de Gasparo; Félix Vargas; Francisco Alba; Ana B. Segarra; Inmaculada Banegas; Manuel Ramı́rez (755-760).
In spite of the well-known contribution of angiotensin II (Ang II) in the pathogenesis of Goldblatt two-kidney one clip (G2K1C) hypertension, the importance of other Ang peptides, such as Ang III, Ang IV or Ang 2–10, is scarcely understood. The functional status of these peptides depends on the action of several aminopeptidases called angiotensinases. The metabolism of Ang III to Ang IV by aminopeptidase M (AlaAP) and of Ang I to Ang 2–10 by aspartyl aminopeptidase (AspAP) was evaluated in the renal cortex and medulla of normotensive (Sham-operated) and hypertensive (G2K1C) rats, treated or not with the AT1 receptor antagonist valsartan. The results demonstrated a highly significant increase of membrane-bound (MEMB) AlaAP in the cortex of the non-ischemic kidney of G2K1C rats compared with the kidney of normal rats and with the clipped kidney of G2K1C rats. This suggests an increased formation of Ang IV in the non-clipped kidney of G2R1C rats. Valsartan reduced MEMB AlaAP and AspAP activities in the renal cortex of normotensive and in the clipped kidney of hypertensive rats. The reduced metabolism of Ang III may prolong its half-life in valsartan-treated animals. These results suggest a role for AlaAP in renovascular hypertension. In addition, the higher AspAP activity of the renal cortex compared to medulla reflects its relative functional difference between both locations.
Keywords: Two-kidney one clip hypertension; Aminopeptidases; Valsartan;
Substance P in the uterine cervix, dorsal root ganglia and spinal cord during pregnancy and the effect of estrogen on SP synthesis by C.N Mowa; S Usip; M Storey-Workley; R Amann; R Papka (761-771).
Prior to parturition the non-pliable uterine cervix undergoes a ripening process (“softens” and dilates) to allow a timely passage of the fetus at term. The exact mechanism(s) triggering and involved in cervical ripening are unknown, though evidence for a role for sensory neurons and their contained neuropeptides is emerging. Moreover, an apparent increase in neuropeptide immunoreactive nerves occurs in the cervix during pregnancy, maternal serum estrogen levels rise at term and uterine cervix-related L6-S1 dorsal root ganglia (DRG) sensory neurons express estrogen receptor (ER) and neuropeptides. Thus, we sought to test the hypothesis that the neuropeptide substance P (SP) changes biosynthesis and release over pregnancy, that estrogen, acting via the ER pathway, increases synthesis of SP in DRG, and that SP is utilized in cervical ripening at late pregnancy. Using immunohistochemistry, in situ hybridization, reverse transcriptase–polymerase chain reaction (RT–PCR) and radioimmunoassay (RIA), we investigated coexpression of ER-α/β and SP; differential expression of ER-α and -β mRNA in DRG neurons; SP synthesis in DRG; and changes in SP concentration in the cervix, DRG and spinal cord over pregnancy. In addition, the effect of exogenous estrogen on SP synthesis in L6-S1 DRG of ovariectomized rats was examined. SP-immunoreactive neurons expressed ER-α and ER-β. SP synthesis (expressed as β-PPT mRNA label) was prominent in small DRG neurons. SP concentration increased in the L6-S1 DRG and spinal cord segments, with a peak at Day 20 of gestation, but decreased in the cervix during the first two trimesters, with a rise over the last trimester to Day 10 levels. SP and ER-α mRNA synthesis increased in DRG over pregnancy but ER-β mRNA levels were largely unchanged. When ovariectomized rats were treated with exogenous estrogen, SP mRNA synthesis in the DRG increased in a dose-related manner, an effect blocked by ER blocker ICI 182 780. From these results, we postulate that synthesis of SP in L6-S1 DRG and utilization in the cervix increase over pregnancy and this synthesis is under influence of the estrogen–ER system, most likely ER-α. We postulate that SP may play a role in cervical ripening and, consequently in the birth process.
Keywords: Parturition; Estrogen; Estrogen receptor; Sensory neurons; Neurogenic inflammation; Pregnant rat;
Inhibition of recombinant dipeptidyl peptidase III by synthetic hemorphin-like peptides by Takehiro Chiba; Yao-Hua Li; Takuya Yamane; Osamu Ogikubo; Muneyoshi Fukuoka; Ryohachi Arai; Sho Takahashi; Takanobu Ohtsuka; Iwao Ohkubo; Nobuo Matsui (773-778).
In order to find the most effective antagonist for dipeptidyl peptidase III degrading enkephalin, we synthesized hemorphin-like pentapeptides with aliphatic or aromatic amino acids at the N-termini, such as VVYPW, LVYPW, IVYPW, YVYPW, FVYPW and WVYPW. Among those pentapeptides, IVYPW and WVYPW showed the strongest inhibitory activity toward rDPP III. The Ki values of IVYPW and WVYPW were 0.100±0.011 and 0.126±0.015 μM (mean±S.E.), respectively. The order of Ki values was Ile≥Trp>Phe≥Tyr>Leu>Ala>Val>Ser>Gly. rDPP III activity is inhibited in a non-competitive manner by these peptides. The peptide VYPW did not inhibit rDPP III activity, but the sequence is essential for the expression of inhibitory activity.
Keywords: Dipeptidyl peptidase III; Enkephalin; Inhibition; Hemorphin-like peptides;
Emotion regulation and touch in infants: the role of cholecystokinin and opioids by Aron Weller; Ruth Feldman (779-788).
Behavioral–pharmacological research in infant rats supports the role of cholecystokinin (CCK) and opioid peptides in mediating early learning of new associations with aspects of the nest and dam, such as maternal odor, milk, and contact. The current paper reviews research that examines the hypothesis that these neuropeptide systems are further involved in mediating emotion regulation in infants, thus playing a role in the emergence of stress-reactivity and other motivational systems. The beneficial effects of maternal proximity, handling, and touch on the development of emotion regulation have been demonstrated in both human and animal models. Interventions that promote tactile stimulation of the infant (“touch therapy”) and infant–mother contact (“skin-to-skin contact” or “kangaroo care”) have been shown to improve the infant’s ability to self-regulate, and to moderate the effects of some risk factors. Theoretical perspectives and empirical findings regarding emotion regulation in infants are first discussed. This is followed by a review of work providing evidence in animal models (and suggestive evidence in humans) for the importance of CCK and opioid neuropeptides in affecting infant emotion regulation and the impact of touch-based interventions, in particular in the context of infant–mother attraction, contact, separation, and attachment.
Keywords: Infants; Emotion regulation; Touch; Cholecystokinin; Opioid neuropeptides; Ultra vocalization; Sheep; Rats; Stress reactivity; Infant–mother attachment; Preterm infants; Self-regulation;