Activation of the lipoxygenase pathway in the methionine enkephalin induced respiratory burst in human polymorphonuclear leukocytes

In comparative studies of f-met-Leu-Phe (FMLP) and methionine enkephalin (ME) induced polymorphonuclear leukocyte (PMNL) stimulation the following results were obtained: (i) both FMLP and ME increased the intracellular killing (IK) capability of human PMNLs probably through NADPH oxidase activation, (ii) the ME-induced respiratory burst (RB) differed from the chemotactic peptide FMLP-triggered superoxide generation because the former was not accompanied by the activation of the glutathione system and the duration of the superoxide production was prolonged. The reaction was dependent on lipoxygenation, was potentiated by indomethacin (IM) and was inhibited by nordihidro-guairetic acid (NDGA), (iii) both 14C-arachidonic acid (14C-AA) release and leukotriene B4 (LTB4) synthesis of ME-treated PMNLs were elevated as compared to those of FMLP triggered cells. Our results suggest that lipoxygenation and even an increased LTB4 synthesis are involved in the ME-induced RB of leukocytes.     

2‐methoxyestradiol inhibits atorvastatin‐induced rounding of human vascular smooth muscle cells

The cardiovascular benefits of statins, including atorvastatin (ATV), have been reported to be gender‐dependent, but the underlying mechanism is unclear. In this study we examine whether estrogen and its metabolite, 2‐methoxyestradiol (2ME), affect the rounding response of human vascular smooth muscle cells (SMCs) induced by ATV. Twenty‐four hour treatment with ATV (10–100 µM) induced rounding of cultured human SMCs. Addition of 2ME (1–20 µM), but not 17β‐estradiol, for 2 h induced re‐spreading of rounded cells. Our further studies showed that the effects of 2ME were mimicked by microtubule‐disrupting drugs and inhibited by taxol. Inhibition of RhoA and ROCK (Rho‐kinase) by C3‐toxin and H‐1152, respectively, blocked 2ME effects. 2ME effects were also blocked by treatment with either actin‐interfering drugs, such as cytochalasin D and jasplakinolide, or myosin inhibitor blebbistatin. ML‐7 and ‐9, the inhibitors for myosin light chain kinase, inhibited 2ME effect as well. ATV treatment induced a decrease of F‐actin content and Thr18/Ser19 dual phosphorylation of myosin regulatory light chain (MRLC), which was rescued by 2ME or mevalonate. The rescue effects of 2ME on F‐actin content and MRLC dual phosphorylation were abolished by taxol or H‐1152. In addition, kinesin Eg5 inhibitor monastrol and dynein inhibitor erythro‐9‐3‐(2‐hydroxynonyl) adenine (EHNA) significantly blocked 2ME effects. Finally, our results revealed that 2ME inhibited the migration of SMCs induced by ATV (0.1 µM) in wound healing assay and Boyden chamber assay. In summary, our data show that 2ME, but not estrogen, inhibits ATV‐induced rounding of human SMCs through induction of microtubule disassembly and activation of the Rho‐ROCK‐actinomyosin pathway. J. Cell. Physiol. 222: 556–564, 2010. © 2009 Wiley‐Liss, Inc.     

Degranulation of mast cells located in median eminence in response to compound 48/80 evokes adrenocortical secretion via histamine and CRF in dogs

The effect of intracerebroventricular infusion of compound 48/80 (C48/80), a mast cell secretagogue, on adrenal cortisol secretion was investigated in dogs under pentobarbital sodium anesthesia. A marked increase in adrenal cortisol secretion was elicited by C48/80 along with a concomitant increase in the plasma levels of cortisol and immunoreactive ACTH, but neither arterial blood pressure and heart rate nor the plasma histamine level altered significantly. Pretreatment with either anti-CRF antiserum or pyrilamine maleate (H(1) histamine-receptor antagonist) significantly attenuated the C48/80-evoked increase in cortisol secretion, but pretreatment with metiamide (H(2)-receptor antagonist) significantly potentiated it. Significant attenuation of the C48/80-evoked increase in cortisol also occurred in dogs given ketotifen, a mast cell stabilizing drug, before pharmacologic challenge. In the pars tuberalis and median eminence (ME), mast cells were highly concentrated in close association with the primary plexus of the hypophysial portal system. Degranulated mast cells were extensively found in the ME of C48/80-treated animals. These results suggest that mast cells located in these regions liberated histamine within the brain as a result of degranulation induced by C48/80 and that this led to activation of the hypothalamic-pituitary-adrenocortical axis.     

Potentiation of cholecystokinin-induced exocrine secretion by either electrical stimulation of the vagus nerve or exogenous VIP administration in the guinea pig pancreas

In the anaesthetized guinea pig, the secretory responses (pancreatic juice flow and protein output) induced by electrical stimulation of the vagus nerve were not blocked by atropine but by hexamethonium. Excitation of the left vagus nerve induced by electrical stimulation significantly potentiated the C-terminal octapeptide of cholecystokinin (CCK-OP)-induced secretory responses. In the isolated perfused pancreas of guinea pig, the secretory responses induced by CCK-OP at concentrations in the physiological range were markedly potentiated by simultaneous stimulation with vasoactive intestinal peptide (VIP). However, the secretory responses induced by CCK-OP at higher concentrations were not potentiated but inhibited by simultaneous stimulation of VIP. The secretory responses induced by carbachol (CCh) at any concentrations were not potentiated but inhibited by simultaneous stimulation of VIP. These results support the view that VIP released from the nerve endings can potentiate the hormonal action of CCK-OP.     

Protective Effects of Mangosteen Extract on H2O2-Induced Cytotoxicity in SK-N-SH Cells and Scopolamine-Induced Memory Impairment in Mice

Mangosteen extracts (ME) contain high levels of polyphenolic compounds and antioxidant activity. Protective effects of ME against β-amyloid peptide (Aβ), induced cytotoxicity have been reported. Here, we further studied the protective effects of ME against oxidative stress induced by hydrogen peroxide (H₂O₂) and polychlorinated biphenyls (PCBs), and demonstrated the protection against memory impairment in mice. The cytoprotective effects of ME were measured as cell viability and the reduction in ROS activity. In SK-N-SH cell cultures, 200 μg/ml ME could partially antagonize the effects of 150 or 300 µM H₂O₂ on cell viability, ROS level and caspase-3 activity. At 200, 400 or 800 µg/ml, ME reduced AChE activity of SK-N-SH cells to about 60% of the control. In vivo study, Morris water maze and passive avoidance tests were used to assess the memory of the animals. ME, especially at 100 mg/kg body weight, could improve the animal’s memory and also antagonize the effect of scopolamine on memory. The increase in ROS level and caspase-3 activity in the brain of scopolamine-treated mice were antagonized by the ME treatment. The study demonstrated cytoprotective effects of ME against H₂O₂ and PCB-52 toxicity and having AChE inhibitory effect in cell culture. ME treatment in mice could attenuate scopolamine-induced memory deficit and oxidative stress in brain.     

Tissue-specific regulation of two functional malic enzyme mRNAs by triiodothyronine

Rat liver malic enzyme (ME) synthesis is known to be regulated by 3,5,3'-triiodo-L-thyronine (T3). Hybridization of 32P-labeled ME cDNA with RNA extracted from normal and T3-induced livers (15 or 50 micrograms/100 g body weight for 10 days) showed an increase in the ME mRNA concentration by approximately 11-fold in T3-treated rats. ME activity and ME mass were stimulated to the same degree as ME mRNA. Northern blot analysis of either total or poly(A+) RNA revealed two distinct ME mRNAs (21 and 27 S) which were equally induced by T3 treatment. Both mRNAs were shown by in vitro translation assay to program the synthesis of the same immunoprecipitable protein corresponding to full-sized ME. From all the above, we concluded that both messages code for active enzyme. ME activity and ME mRNA were also detected in nonhepatic tissues for which different responses to T3 induction were observed without direct correlation with their respective content of T3 nuclear receptor. Increases in ME activity and level of hybridizable ME mRNA were seen 48 h after a single administration of T3 (200 micrograms/100 g body weight) in liver, kidney, and heart (10.3- and 15.5-, 1.7- and 2.6-, and 1.72- and 3.4-fold above basal values, respectively). Lower levels of induction could already be detected after 24 h, liver being the most stimulated tissue. ME was not affected in brain, lung, testis, and spleen. Northern blot analysis showed that both ME mRNAs are present in all tissues tested, although in different relative proportions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toxoplasma gondii genotype determines MyD88-dependent signaling in infected macrophages

Infection of mouse macrophages with Toxoplasma gondii elicits MAPK activation and IL-12 production, but host cell signaling pathways have not been clearly delineated. Here, we compared macrophage signaling in response to high virulence type I (RH) vs low virulence type II (ME49) strain infection. Tachyzoites of both strains induced p38 MAPK-dependent macrophage IL-12 release, although ME49 elicited 2- to 3-fold more cytokine than RH. IL-12 production was largely restricted to infected cells in each case. RH-induced IL-12 release did not require MyD88, whereas ME49-triggered IL-12 production was substantially dependent on this TLR/IL-1R adaptor molecule. MyD88 was also not required for RH-stimulated p38 MAPK activation, which occurred in the absence of detectable upstream p38 MAPK kinase activity. In contrast, ME49-driven p38 MAPK activation displayed an MyD88-dependent component. This parasite strain also induced MyD88-dependent activation of MKK4, an upstream activator of p38 MAPK. The results suggest that RH triggers MAPK activation and IL-12 production using MyD88-independent signaling, whereas ME49 uses these pathways as well as MyD88-dependent signaling cascades. Differences in host signaling pathways triggered by RH vs ME49 may contribute to the high and low virulence characteristics displayed by these parasite strains.     

Effect of menthol in experimentally induced ulcers: Pathways of gastroprotection

Based on ethnopharmacological indications that Mentha species may be used in the treatment of gastrointestinal diseases, this study aimed to characterize the gastroprotective mechanisms of menthol (ME), the major compound of the essential oil from species of the genus Mentha. The gastroprotective action of ME was analyzed in gastric ulcers that were induced by ethanol or indomethacin in Wistar male rats. The mechanisms responsible for the gastroprotective effect were assessed by analyzing the amount of mucus secreted, involvement of non-protein sulfhydryl (NP-SH) compounds, involvement of calcium ion channels and NO/cGMP/K⁺_ATP pathway, gastric antisecretory activity and the prostaglandin E₂ (PGE₂) production. The anti-diarrheal activity and acute toxicity of ME were also evaluated. Oral treatment with ME (50 mg/kg) offered 88.62% and 72.62% of gastroprotection against ethanol and indomethacin, respectively. There was an increased amount of mucus and PGE₂ production. The gastroprotective activity of ME involved NP-SH compounds and the stimulation of K⁺_ATP channels, but not the activation of calcium ion channels or the production of NO. The oral administration of ME induced an antisecretory effect as it decreased the H⁺ concentration in gastric juice. ME displayed anti-diarrheal and antiperistaltic activity. There were no signs of toxicity in the biochemical analyses performed in the rats’ serum. These results demonstrated that ME provides gastroprotective and anti-diarrheal activities with no toxicity in rats.     

Ethanol and acetaldehyde potentiate the clastogenicity of ultraviolet light, methyl methanesulfonate, mitomycin C and bleomycin in Chinese hamster ovary cells

Ethanol itself did not induce any apparent chromosome aberrations in Chinese hamster ovary cells. However, posttreatment with ethanol potentiated the chromosome aberrations induced by ultraviolet light (UV), methyl methanesulfonate (MMS), mitomycin C (MMC) or bleomycin (BLM). Chromatid exchanges were predominantly increased in cultures treated with UV, MMS or MMC and then with ethanol, whereas chromosome breaks and chromatid exchange were the major types of aberrations increased in the cultures treated with BLM and ethanol. Posttreatment with acetaldehyde, the major metabolite of ethanol, also potentiated the chromosome aberrations induced by UV, MMS, MMC or BLM. The main types of aberrations potentiated by posttreatment with acetaldehyde were similar to those by posttreatment with ethanol.     

Electrophysiological effects of enkephalin analogs in rat cortex.

The microiontophoretic potencies of methionine-enkephalin (ME) analogs with similar charges but different potencies in the $\text{in vitro}$ assays were studied with respect to spontaneous and evoked activity of rat cerebral cortex neurons (CX). ME slowed discharge in 65% of the 62 CX tested; activity evoked by acetylcholine (ACh) or glutamate, as well as spontaneous discharge, was affected. The vast majority of responsive cells were deeper than 500 μ and excited by ACh. Antidromic spikes were elicited in many of these neurons by pyramidal tract stimulation. The electrophysiological effects of D-Ala² ME amide, a more potent analog $\text{in vitro}$, was similar to ME when tested on the same parietal CX, however, D-Ala² ME amide was much more potent than ME on frontal CX. On the other hand N-acetyl D-Ala²-Lys³ ME amide, which has low potency $\text{in vitro}$, had little effect on CX which were readily depressed by equivalent doses of ME or the D-Ala² analog. The depressions induced by ME or the D-Ala² derivative were readily and reversibly antagonized by prior iontophoretic administration of naloxone. It is concluded that opiate receptor interactions may play an important role in electrophysiological responses to iontophoretically administered ME and that the deeper cholineceptive cortical cells, possibly pyramidal neurons, may be preferentially affected.     

Post-treatments with sodium arsenite during G2 enhance the frequency of chromosomal aberrations induced by S-dependent clastogens

Treatment with sodium arsenite during the G2 phase potentiated the chromatid breaks and chromatid exchanges induced by ultraviolet light or 4-nitroquinoline 1-oxide but not those induced by methyl methanesulfonate, ethyl methanesulfonate, mitomycin C or cisplatin in Chinese hamster ovary cells. A comparison was made between the effects of treatment during G2 with sodium arsenite, cytosine-β- -arabinofuranoside, aphidicolin, hydroxyurea, caffeine, 3-aminobenzamide and novobiocin on the frequency of chromosomal aberrations induced by the above-mentioned S-dependent clastogens. It was found that the effects varied considerably, both quantitatively and qlalitatively. However, potentiation was more often observed in the chromosomal aberrations induced by ultraviolet light and 4-nitroquinoline 1-oxide than by other S-dependent clastogens, and the frequency of chromatid exchanges was potentiated only in cells pretreated with ultraviolet light or 4-nitroquinoline 1-oxide. Furthermore, for all of the S-dependent clastogens studied, treatment with cytosine-β- -arabinofuranoside during the G2 phase potentiated the frequency of chromatid breaks but not the frequency of chromatid exchanges.     

Bidirectional effect of met-enkephalin on macrophage effector functions

Summary Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10^-9-10^-7 M) antibody dependent cellular cytotoxicity (ADCC)was markedly stimulated with a simultaneous decrease of Fc receptor (FcR) mediated phagocytosis while the opposite was observed at 10^-6-10^-5 M concentrations.Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na⁺ influx which was followed by a Ca²⁺ efflux in the range of low concentrations. In the range of high concentrations Na⁺ influx was accompanied by a Ca²⁺ influx. (2) ME at 10^-8 M concentration induced a rise in cGMP level with a plateau in the 60–120th min of incubation. This effect was prevented by 10^-5 M of naloxone. At 10^-6 M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10^-6 M abolished both the Ca²⁺ influx and the rise in cAMP level induced by 10^-6-10^-5 M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10^-6-10^-5 M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca²⁺ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.     

In vivo measurements of the cerebral perfusion and cardiovascular effects of the novel guanidine ME10092 in the non-human primate, Papio ursinus

The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the first time pharmacological effects of ME10092 in the primate, viz. the Cape baboon Papio ursinus. The effects of ME10092 (1 and 2 mg/kg doses) on the cerebral blood flow, heart rates and the systolic and diastolic blood pressure were investigated after intravenous injection to the baboon under anaesthesia. The cerebral perfusion effects of ME10092 were assessed using Single Photon Emission Computed Tomography according to the split-dose approach and 99mTc-hexamethyl-propylene amine oxime as brain perfusion tracer. The observation that the recovery times from the anaesthesia were unacceptably prolonged excluded doses beyond 2 mg/kg. The data indicate that no cerebral perfusion changes were induced at both the 1 and 2 mg/kg doses of ME10092. Both these doses of ME10092 showed blood pressure and heart rate effects, with the latter being more significant. Decreases in heart rate were seen directly after ME10092 administration reaching levels of about 20% for the 2 mg/kg dose and about 15% for the 1 mg/kg dose at around 6 min post drug administration. A transient decrease in both systolic and diastolic blood pressure was observed for the higher dose. The blood pressure data further suggest an attenuation of the anaesthesia induced increase in pressure usually present in non-intervention studies. ME10092 clearly exhibits mycocardial effects in the non-human primate, similar to the effects previously observed in the ischaemia-reperfusion rat model, where ME10092 showed strong protection.     

p38 Mitogen-activated protein kinases is required for counteraction of 2-methoxyestradiol to estradiol-stimulated cell proliferation and induction of apoptosis in ovarian carcinoma cells via phosphorylation Bcl-2

INTRODUCTION: 2-Methoxyestradiol (2ME2), a natural endogenous product of estradiol (E2) metabolism, has been shown to be a selective apoptotic agent for cancer cells but not for normal cells. In this study, we determined that 2ME2 counteracts E2-stimulated cell growth and induces apoptosis in ovarian carcinoma cells. In addition, we demonstrate that 2ME2 induces apoptosis via p38 and phospho-Bcl2 pathway. METHODS: 2ME2 and/or E2 were administered to the OVCAR-3 (human ovarian cancer) cell line. Cell growth inhibition was analyzed by [3H] Thymidine incorporation assay and DNA fluorometric assay. Cell apoptosis was tested by DNA fragmentation analysis and FACS. The signaling pathway was determined by a series of biochemical assays. RESULTS: 2ME2 inhibited estradiol-stimulated cell growth and induced apoptosis in an ovarian carcinoma cell line. MAPK and p38, but not JNK, were found to be critical mediators in this process. Expression of a dominant negative mutant of p38 kinase or p38 specific inhibitor, SB 203580, almost completely blocked the process. Furthermore, Bcl-2 phosphorylation was required for 2ME2-induced effects. CONCLUSION: Our data suggest that 2ME2 inhibits E2-stimulated proliferation and induces apoptosis in ovarian carcinoma cells. Furthermore, activation of p38 and phosphorylation of Bcl-2 plays a critical role in the mechanism. 2ME2 therefore, may have a clinical application for the treatment of ovarian cancer.     

Immunocytochemistry of luteinizing hormone-releasing hormone during spontaneous and thyroxine-induced metamorphosis of bullfrogs

Double-bridge peroxidase-antiperoxidase immunocytochemistry was used to compare the developmental appearance of immunoreactive LH-RH (ir-LH-RH) in brains of bullfrog (Rana catesbeiana) tadpoles during either spontaneous or thyroxine-induced metamorphosis. During spontaneous metamorphosis, ir-LH-RH was localized in fibers of the external layer of the median eminence (ME) of stage XIII-XXV animals, while immunoreactive perikarya and other immunostained brain structures were absent. The extent and intensity of ME immunostaining increased concomitantly with measured ME morphological development. Tadpoles induced with thyroxine to metamorphic stages XIX-XXI exhibited ME structural development and neurohypophysial neurosecretory staining similar to spontaneously metamorphosed individuals of equal stages. However, comparable ME ir-LH-RH immunostaining and gonadal size were both less developed in thyroxine-treated animals, although increased relative to non-metamorphic vehicle-injected controls. These results indicate that the hypothalamic LH-RH system changes concurrently with ME structural development during spontaneous metamorphosis. Reduced ME ir-LH-RH staining and gonadal size in thyroxine-treated animals suggest that during prometamorphosis, factors other than thyroxine alone may coordinate the normal maturation of the hypothalamo-pituitary-gonadal axis of the bullfrog.     

2‐methoxyestradiol‐mediated anti‐tumor effect increases osteoprotegrin expression in osteosarcoma cells

Osteosarcoma is a bone tumor that frequently develops during adolescence. 2‐Methoxyestradiol (2‐ME), a naturally occurring metabolite of 17β‐estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2‐ME actions, we studied the effect of 2‐ME treatment on OPG gene expression in human osteosarcoma cells. 2‐ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2‐ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3‐, 1.9‐, 2.8‐, and 2.5‐fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2‐ME treatment. The effect of 2‐ME on osteosarcoma cells was ligand‐specific as parent estrogen, 17β‐estradiol and a tumorigenic estrogen metabolite, 16α‐hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, co‐treating osteosarcoma cells with OPG protein did not further enhance 2‐ME‐mediated anti‐tumor effects. OPG‐released in 2‐ME‐treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2‐ME‐mediated anti‐proliferative effects in osteosarcoma cells, but rather participates in anti‐resorptive functions of 2‐ME in bone tumor environment. J. Cell. Biochem. 109: 950–956, 2010. © 2010 Wiley‐Liss, Inc.     

Influence of the position of the side chain hydroxy group on the gastric antisecretory and antiulcer actions of E1 prostaglandin analogs.

The influence of transposing the C-15 hydroxy group of prostaglandin E1 methyl ester (PGE2ME) on gastric antisecretory and antiulcer actions was investigated. The compound (+/-)15-deoxy- 16alpha, beta-hydroxy PGE1ME (SC-28904) was equipotent to the reference standard PGE1ME in suppressing histamine-stimulated gastric secretion in the Heidenhain pouch (HP) dog. In contrast to PGE1ME, SC-28904 was longer acting when administered intravenously and also showed significant oral activity in the histamine-stimulated gastric fistula dog. SC-28904 was also equipotent to PGE1ME (range of active doses of 0.5 to 5.0 mg/kg, s.c.) in inhibiting forced-exertion gastric ulceration in rats. The compound (+/-)15-deocy-17alpha, beta-hydroxy PGE1ME (SC-30963) was an inactive antisecretory agent in the dog at the 1.0 mg/kg i.v. bolus dose. This dose was 100 times greater than the active antisecretory dose of PGE1ME. Likewise, SC-30693, when administered subcutaneously at a 5.0 mg/kg dose, was also totally inactive in preventing gastric ulcers induced by forced exertion in rats. The important implications of this work are that some of the receptor sites for the PGE1 molecule could easily accomodate the side chain hydroxy group either in the C-15 or C-16 position. Moreover, the hydroxy group in the latter position significantly improved the biological activity of PGE1ME.     

Potentiation of histamine release by sodium cromoglycate.

Human lung slices passively sensitized with allergic serum released histamine when incubated with specific antigen and anti-IgE but anti-IgG had no effect. Sodium cromoglycate (SCG) inhibited antigen induced histamine release but the dose-response curve was bell-shaped. Inhibition of anti-IgE induced release was linearly related to dose, whereas that induced by anti-IgG was potentiated by increasing doses of SCG. After sensitization with allergic serum in which IgE had been inactivated by heating, specific antigen released little or no histamine but this was potentiated by SCG. It is concluded that SCG inhibits IgE mediated but potentiates IgG mediated allregic reactions thus explaining its characteristic dose-response curve $\text{in vitro}$.     

Secretin N-terminal hexapeptide potentiates insulin release in mouse islets

Peptides representing the N-terminal part of secretin were synthesized and their effects tested on column-perifused isolated mouse pancreatic islets. Insulin release induced by D-glucose was potentiated by the two peptides His-Ser-Asp-Gly-Thr-Phe-OMe (S1-6) and Ser-Asp-Gly-Thr-Phe-OMe (S2-6). The consecutive smaller N-terminal peptides Asp-Gly-Thr-Phe-OMe (S3-6) and Gly-Thr-Phe-OMe (S4-6) had no effects while the dipeptide ester Thr-Phe-OMe (S5-6) also potentiated the release of insulin. The results suggest that the N-terminal part of secretin may be involved in the marked in vitro glucose-dependent insulin release induced by secretin.