Effects of methionine enkephalin on immune enhancement by reducing myeloid derived suppressor cells and reprogramming liver metabolism in colon cancer mice

OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg^(-1) for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TG test kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure m RNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTS MENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4^+T and CD8^+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TG and T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL^(-1)β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.

EFFECT OF METHIONINE ENKEPHALIN ON MIGRATION OF MACROPHAGES FROM MICE WITH IMPAIRED LIVER

Objective To observe the effects of methionine enkephalin (M Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. Methods Liver of mice was impaired by feeding CCl 4 and macrophage migration inhibitory factor (MMIF) was produced by Con A stimulated spleen lymphocytes. Inhibition of macrophage migration was measured in reaction system by adding M Enk. Results Migration of macrophages in both liver impaired and control group were suppressed by MMIF, but the suppression might be reversed by adding 1 μmol/L M Enk ( P <0.05).M Enk could significantly inhibit in vitro both of the combination of MMIF with macrophages and production of MMIF from lymphocytes ( P <0.01).Macrophages from liver imparied group showed a higher sensitivity compared to the control group ( P <0.05).Conclusion The study suggests that opioid peptieds play an important role in the modulation of the immune response under stress as liver impairment.

Determination of Carbon and Nitrogen Isotope Fractions in Asparagine, Aspartic Acid, Threonine and Methionine

The nomenclature for compounds that are modified with isotopes is growing every day. Compounds can be modified with isotopes either individually, in a functional group or groups, or completely with all atomic centers of the element. This diversity of isotope-modified compounds increases the range of researches that can be studied using them. Compounds modified with isotopes of carbon-13 or nitrogen-15 can be converted into carbon monoxide, carbon dioxide and molecular nitrogen. Currently, only the average value of carbon-13 or nitrogen-15 isotopes can be determined. However, by directly determining the atomic share of these isotopes in organic compounds modified with isotopes, information about the isotopic centers of the element can be obtained. The atomic fraction of an element is defined as a single carbon or nitrogen isotope-modified center or centers, or all centers that are isotope-modified with that element at the same time. Carbon-13 or nitrogen-15 isotopes’ atomic fraction can be determined molecularly or with fragment ions of different elemental content, or both. This makes the method self-verifying, increasing the accuracy and reliability of the results obtained. Amino acids, such as asparagine, aspartic acid, methionine, and threonine, are essential for the human body. This proposed method of isotopic analysis will increase the possibilities for scientific research using these compounds.

Feeding Practices and Use of Lysine and Methionine in Pigrationing on Intensified Pig Breeding in the West Center and Hauts Bassins Regions of Burkina Faso

The aim of the study was to assess feeding practices and the use of lysine and methionine in pig rationing on intensified and semi-intensive pig breeding in the Koudougou and Bobo-Dioulasso areas. To this end, a cross-sectional survey was carried out on 87 breeding in these towns. A Discriminant Factorial Analysis (DFA) confirming a k-means classification of the data collected was used to retain 71 breeding divided into three breeding classes: Class A (32.4% of breeding), Class B (14.08%) and Class C (53.52%). The results show that the majority of pig breeders were men between the ages of 36 and 59. Average herd sizes were 35 ± 28;79 ± 42 and 89 ± 21 pigs for Classes A, B and C respectively. The main breeds of pig found on the breeding were crossbred, Large white, local, Landrace and Duroc. Class A (26.1%), B (30%) and C (15.8%) breeders were familiar with both lysine and methionine. Class A breeders distributed feed staggered (65.2%) and in rations (34.8%). Lysine (13%) and methionine (8.7%) were purchased at 5250 FCFA/kg. Those in class B distributed feed staggered (50%) and in the form of rations (50%), in which they incorporated lysine (30%) and methionine (30%) purchased at a cost of 2500 FCFA/kg and 3000 FCFA/kg respectively. Rationing and staggered feeding were practiced by 23.7% and 76.3% of Class C breeders respectively. Only lysine purchased at 3400 FCFA/kg was incorporated into rations by 10.5% of breeders. The high cost of lysine and methionine was incriminated by Class A (100%), B (33.3%) and C (50%) breeders. In conclusion, intensive pig breeding, the practice of rationing and the incorporation of the amino acids lysine and methionine are of ascending importance from classes C, A to B. The high cost of feedstuffs, particularly lysine and methionine, compromises their use in rations, which could have a negative impact on expected breeding performance. The screening and use of feeds rich in and/or enriched with these amino acids, through the development or adaptation of technologies, could improve the efficiency of rations and the productivity of intensive pig breeding in Burkina Faso.

Midbrain enkephalin expression in a rat migraine model following intragastric scorpion powder administration

Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine at mRNA and protein levels. Results confirmed that migraine rat abnormal behavior was significantly improved, and proenkephalin mRNA expression was significantly increased following treatment with scorpion. The number of methionine-enkephalin- positive cells in the migraine rats following treatment with scorpion was significantly increased, but no significant difference in the number of leucine-enkephalin-positive cells was detectable compared with migraine and normal rats. Taken together, these results show that scorpion exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine rats.

Effects of Toutongning capsule on enkephalin expression in a rat migraine headache model

Toutongning capsule is used for the treatment of migraine headaches, and has yielded therapeutically beneficial effects. However, whether Toutongning capsule exerts its effects via endogenous opioid peptides remains poorly understood. This study investigated the effects of Toutongning capsule on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine headache at the mRNA and protein levels. Results confirmed that proenkephalin mRNA levels were significantly upregulated following treatment with Toutongning capsule. The numbers methionine-enkephalin and leucine-enkephalin-positive cells were significantly greater in the migraine headache rats following treatment with Toutongning capsule compared with the model group. Taken together, these results show that Toutongning capsule exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine headache rats.

Effects of methionine treatment on storage quality and antioxidant activity of postharvest jujube fruit

Jujube fruits usually suffer from physiological disorders or infectious diseases during storage,leading to quality deterioration,softening,or rotting.Therefore,this study aims to investigate the effect of methionine soaking treatment on the postharvest jujube fruit decay rate and storage quality.Methionine treatment significantly reduced the decay rate of postharvest jujube fruit and effectively maintained fruit color and titratable acid.Methionine treatment effectively delayed the decrease of firmness,soluble solids,ascorbic acid,and lignin contents in jujube fruit.Methionine treatment reduced the content of alanine and phenylalanine,and increased the content of glycine in jujube fruit,but displayed no significant effect on total amino acid content.In addition,jujube fruits in the methionine treatment group had a higher total phenolic and flavonoid content and antioxidant capacity,both in free and bound forms.Compared with the control,methionine treatment also significantly increased the content of individual phenolic acid fractions(gallic acid,vanillic acid,and syringic acid)and flavonoid fractions(catechin,epicatechin,rutin)in free form as well as individual phenolic acid fractions in bound form(gallic acid and ferulic acid)in jujube fruits.Overall,this study suggested that the methionine treatment could be used as a prospective preservative to reduce the postharvest decay of jujube fruit and alleviate its nutritional quality deterioration during cold storage at 4°C.

Lipid metabolism and m^(6)A RNA methylation are altered in lambs supplemented rumen-protected methionine and lysine in a low-protein diet

Background:Methionine or lysine has been reported to influence DNA methylation and fat metabolism,but their combined effects in N6-methyl-adenosine(m^(6)A)RNA methylation remain unclarified.The combined effects of rumen-protected methionine and lysine(RML)in a low-protein(LP)diet on lipid metabolism,m^(6)A RNA methylation,and fatty acid(FA)profiles in the liver and muscle of lambs were investigated.Sixty-three male lambs were divided into three treatment groups,three pens per group and seven lambs per pen.The lambs were fed a 14.5%crude protein(CP)diet(adequate protein[NP]),12.5%CP diet(LP),and a LP diet plus RML(LP+RML)for 60 d.Results:The results showed that the addition of RML in a LP diet tended to lower the concentrations of plasma leptin(P=0.07),triglyceride(P=0.05),and non-esterified FA(P=0.08).Feeding a LP diet increased the enzyme activity or m RNA expression of lipogenic enzymes and decreased lipolytic enzymes compared with the NP diet.This effect was reversed by supplementation of RML with a LP diet.The inclusion of RML in a LP diet affected the polyunsaturated fatty acids(PUFA),n-3 PUFA,and n-6 PUFA in the liver but not in the muscle,which might be linked with altered expression of FA desaturase-1(FADS1)and acetyl-Co A carboxylase(ACC).A LP diet supplemented with RML increased(P<0.05)total m^(6)A levels in the liver and muscle and were accompanied by decreased expression of fat mass and obesity-associated protein(FTO)and alk B homologue 5(ALKBH5).The m RNA expressions of methyltransferase-like 3(METTL3)and methyltransferase-like 14(METTL14)in the LP+RML diet group were lower than those in the other two groups.Supplementation of RML with a LP diet affected only liver YTH domain family(YTHDF2)proteins(P<0.05)and muscle YTHDF3(P=0.09),which can be explained by limited m^(6)Abinding proteins that were mediated in m RNA fate.Conclusions:Our findings showed that the inclusion of RML in a LP diet could alter fat deposition through modulations of lipogenesis and lipolysis in the liver and muscle.These changes in fat metabolism may be associated with the modification of m^(6)A RNA methylation.

Serotonin样,Substance P样,Enkephalin样反应阳性神经元胞体在大鼠中缝核簇内的分布

本文用PAP法研究了Serotonin样,Substance P样,Leucine—Enkephalin样和Methionine—Enkephalin样反应阳性神经元胞体在大鼠中缝核簇内的分布。证明Serotonin存在于中缝苍白核、中缝隐核、中缝大核、中缝桥核、中央上核和中缝背核等处的某些神经元胞体内。以中、小细胞为主,在中缝大核内有少数大细胞。细胞形态为梭形、圆形、卵圆形以及多极细胞。Substance P样反应阳性胞体在上述中缝核内也被发现,其胞体的大小、形态和分布与serotonin样反应阳性胞体相似,但数目稍少。Leucine—Enkephalin样反应阳性胞体存在于中缝苍白核、中缝隐核、中缝大核、中缝桥核、中缝背核和中央上核内,但Methionine—Enkephalin样反应阳性细胞体仅在中缝苍白核和中缝隐核的吻侧部以及中缝大核内发现。后两者均以大,中型多极细胞为主。

EFFECTS OF ACUPUNCTURE ON THE CONTENTS OF ENKEPHALINS IN DIFFERENT BRAIN REGIONS AND CORTICOSTERONE IN PLASMA OF RATS WITH ENDOTOXIN SHOCK

In this experiment,we have observed the effects of acupuncture on the contents ofenkephalins in different brain regions and corticosterone in plasma of rats with endotoxin shock.Theresults showed that after acupuncture the endogenous enkephalins were significantly decreased(P【0.05)in the midbrain and brain stem of endotoxin shock rats,suggesting the anti-shock of acupuncture might be related to the enkephalins in the midbrain and brain stem.In addition,there was a rising trend in plasma corticosterone of the rats with toxic shock.

Analgesic action of suspended moxibustion in rats with chronic visceral hyperalgesia correlates with enkephalins in the spinal cord

Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.

Peripartal rumen-protected methionine supplementation to higher energy diets elicits positive effects on blood neutrophil gene networks, performance and liver lipid content in dairy cows

Background： Main objectives were to determine to what extent Smartamine M（SM） supplementation to a prepartal higher-energy diet could alter neutrophil（PMN） and liver tissue immunometabolic biomarkers, and whether those responses were comparable to those in cows fed a prepartal lower-energy diet（CON）.Results： Twenty-eight multiparous Holstein cows were fed CON（NEL= 1.24 Mcal/kg DM） during d-50 to d-22 relative to calving. From d-21 to calving, cows were randomly assigned to a higher-energy diet（OVE, n = 9; NEL= 1.54 Mcal/kg DM）, OVE plus SM（OVE ＋ SM, n = 10; SM = 0.07 % of DM） or remained on CON（n = 9）. Al cows received the same basal lactation diet（NEL= 1.75 Mcal/kg DM）. Supplementation of SM（OVE ＋ SM） continued until 30 d postpartum. Liver biopsies were harvested at d-10, 7, and 21 relative to parturition. Blood PMN isolated at-10, 3, and 21 d relative to calving was used to evaluate gene expression. As expected, OVE increased liver lipid content postpartum; however,cows fed OVE ＋ SM or CON had lower concentrations than OVE. Compared with OVE, cows in CON and OVE ＋ SM had greater DMI postpartum and milk production. Furthermore, cows fed OVE ＋ SM had the greatest milk protein and fat percentage and lowest milk SCC despite having intermediate PMN phagocytic capacity. Adaptations in PMN gene expression in OVE ＋ SM cows associated with the lower SCC were gradual increases from-10 to 21 d in genes that facilitate migration into inflammatory sites（SELL, ITGAM）, enzymes essential for reducing reactive oxygen metabolites（SOD1, SOD2）, and a transcription factor（s） required for controlling PMN development（RXRA）. The greater expression of TLR4 on d 3, key for activation of innate immunity due to inflammation, in OVE compared with CON cows suggests a more pronounced inflammatory state. Feeding OVE ＋ SM dampened the upregulation of TLR4, despite the fact that these cows had similar expression of the pro-inflammatory genes NFKB1 and TNF as OVE. Cows in CON had lower overall expression of these inflammation-related genes and GSR, which generates reduced glutathione, an important cellular antioxidant.Conclusions： Although CON cows appeared to have a less stressful transition into lactation, SM supplementation was effective in alleviating negative effects of energy-overfeeding. As such, SM was beneficial in terms of production and appeared to boost the response of PMN in a way that improved overall cow health.

Immunomodulating effects of methionine enkephalin

甲硫氨酸脑啡肽（ＭｅｔＥｎｋ）在神经免疫内分泌调节网络中的作用引起广泛关注．作者等实验证明它能使ＬＰＳ刺激的小鼠腹腔巨噬细胞产生ＩＬ１，纳洛酮不能阻止这种作用．ＭｅｔＥｎｋ促进小鼠脾淋巴细胞增殖和ＩＬ２、ＩＬ６的产生，这种上调作用与增强此二种白细胞介素ｍＲＮＡ转录并提高其稳定性有关．因此ＭｅｔＥｎｋ在增强前炎性细胞因子表达方面是一个重要的免疫调节信号分子．

Influence of Methionine Supplementation in Chelation of Lead in Rats1

The influence of methionine supplementation on the efficacy of common antidotes to lead poisoning, calcium disodium ethylenediaminetetraacetate (CaNa_2EDTA) and D-penicillamine (DPA), was investigated in rats. The animals were given lead acetate (0.1% in drinking water) for 12 weeks and thereafter treated with CaNa_2EDTA, DPA (0.3mmol/kg, intraperitoneally), DL-methionine (1.34 mmol/kg, intragastrically), or the combination of a chelating agent and methionine for 3 days. While chelating agents enhanced the urinary excretion of Pb, methionine increased the fecal excretion of Pb significantly. Treatment with the combination of a chelating agent and methionine did not potentiate the effect of each antidote. However, methionine supplementation increased the efficacy of both chelating agents in reducing the hepatic and renal Pb burden but not the blood Pb level. The Pb-induced inhibition of blood δ-aminolevulinic acid dehydratase activity and the increase in urinary excretion of δ-aminolevulinic acid were reversed to a certain extent by CaNa_2EDTA, DPA, and methionine but the combination did not improve their individual performances. The beneficial effects of methionine may be attributed to its ability to increase the bioavailability of glutathione (GSH), useful in chelating Pb and counteracting the toxic effects, as evidenced by restoration of the Pb-induced decrease in hepatic GSH level by treatment with methionine. Methionine may be useful as a supportive therapy in chelation of Pb. (c)1989 Academic Press. Inc.

Effects of electric field stimulation on endogenous enkephalin content in artery wall

After 20min electric field stimulation,L-enkephalin （L-ENK） content in the rabbitear artery declined from the control value of 38.99±17.29 to 12.55±1.96pg/mg of wet tissue（n=12）,and M-enkephalin （M-ENK） content from 134.67±8.11 to 73.68±17.96pg/mg of wet tis-sue （n=6）,both being significantly decreased.This effect was not influenced after blockade ofadrenergic receptor by yohimbine.Contractions of artery strips induced by electric field stimulationwere enhanced distinctly after pretreatment of the artery strips with naloxone,an opioid receptorblocker,and with pronase,but not after pretreatment with trypsin.The results suggested that the re-lease of endogenous enkephalins in the ear artery could be induced by electric field stimulation andx2-receptor might not participate in the release course,The release amount of ENK from the ar-terv strips increased when the stimulus freduency increased within the range of 2 Hz to 8 Hz.

Plasma leucine enkephalin content in patients with “Liver-blood deficiency” syndrome and clinical significance

Ｐｌａｓｍａｌｅｕｃｉｎｅｅｎｋｅｐｈａｌｉｎｃｏｎｔｅｎｔｉｎｐａｔｉｅｎｔｓｗｉｔｈ“Ｌｉｖｅｒｂｌｏｏｄｄｅｆｉｃｉｅｎｃｙ”ｓｙｎｄｒｏｍｅａｎｄｃｌｉｎｉｃａｌｓｉｇｎｉｆｉｃａｎｃｅＳＨＩＬｉｎＪｉｅ１，ＣＨＥＮＧｕｏＬｉｎ１，Ｌ...

Conceptual Density Functional Theory Study of the Chemical Reactivity Properties and Bioactivity Scores of the Leu-Enkephalin Opioid Peptide Neurotransmitter

The SMD solvation model (Solvation Model based on the Density) and eight density functionals, CAM-B3LYP, LC-ωPBE, M11, MN12SX, N12SX, ωB97, ωB97X, and ωB97XD, were assessed in link with the Def2TZVP basis set for the calculation of the structure of the Leu-Enkephalin Opioid Peptide Neurotransmitter as well as their molecular properties. Through the Conceptual Density Functional Theory (CDFT), the entire chemical descriptors for the system were calculated. The active regions of the molecules necessary for electrophilic, nucleophilic and radical attacks were chosen through linking them with the corresponding Fukui functions. Furthermore, the prediction of the pKa value for the peptide is done with great accuracy as well as the ability of the studied molecule in acting as an efficient inhibitor of the formation of Advanced Glycation Endproducts (AGEs), which comprises of a useful knowledge for the development of drugs for preventing Alzheimer, Diabetes and Parkinson diseases. Lastly, the bioactivity scores for the studied peptides are predicted via various methodologies.

Increased susceptibility to experimental steatohepatitis induced by methionine-choline deficiency in HBs-Tg mice

BACKGROUND: Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However, no animal model of nonalcoholic steatohepatitis associated with HBV infection is available, and the influence of viral infection on nutritional hepatic steatosis is unclear. METHODS: We used HBV surface antigen transgenic mice (HBs-Tg mice), which mimic healthy human carriers with hepatitis B surface antigen. The mice were fed with a high-fat methionine-choline-deficient diet (MCD) to build a reliable rodent nutritional model of nonalcoholic steatohepatitis associated with HBV infection, and the changes in body weight and serum triglycerides were measured. Hepatocyte ballooning changes were determined by hematoxylin and eosin staining. The extent of hepatic fat accumulation was evaluated by oil red O staining. Immunohistochemical assays were performed to detect proliferating cell nuclear antigen as an index of cell proliferation. RESULTS: MCD feeding provoked systemic weight loss and liver injury. MCD feeding caused more macrovesicular fat droplets and fat accumulation in the livers of HBs-Tg mice than in wild-type C57BL/6 mice. In addition, within 30 days of MCD exposure, more PCNA-positive nuclei were found in the livers of HBs-Tg mice. CONCLUSIONS: HBs-Tg mice fed with a lipogenic MCD form more macrovesicular fat droplets earlier, coincident with more hepatocyte proliferation, resulting in the appearance of increased susceptibility to experimental steatohepatitis in these mice.

Effects of Coated Methionine on the Growth Performance, Blood Biochemical Indices and Nutrient Apparent Ileal Digestibility in Broilers

[ Objective] This trial was conducted to study the effects of different coated methionines on the growth performance, blood biochemical indices and apparent ileal digestibility of amino acids in broilers. [ Method ] A total of 3 780 Cobb 500 broilers aged 18 days were randomly arranged into 7 groups with 3 replicates per group and 180 broilers per replicate. Control group （A） received the basal diet supplemented with O. 16% DL-me- thionine, and trial groups received the basal diets supplemented with 0.32% （ B）, 0.29% （ C）, 0.26% （ D）, 0.22% （ E）, 0.19% （F） and 0.16% （G） of coated methionine, and broilers were fed to the age of 42 days. ＂[ Result] The final weight, average daily gain and average daily feed intake of groups B and C were higher than those of the control group （ P〈0.05）, and the mortality of group B was lower than that of the control group （ P 〈0.05）, but there was no significant difference in all above indices between the other groups and the control group （P 〉 0.05）. Plasma GSH-Px activity of trial groups （ except group G） was higher than that of the control group （ P 〈 0.05）, and SOD activity of groups B and C were higher than that of group G （P 〈0.05）, but there were no significant differences in other blood biochemical indices among all groups （P 〉0.05）. There were no significant differences in apparent ileal digestibility of dry matter and crude protein between trial groups and the control group （ P 〉0.05 ）, and the apparent ileal digestibility of amino acids of trial groups was increased （P 〈0.05） or no change expect that the apparent ileal digestibility of many kinds of amino acids of group G was decreased compared with the control group （P〈0.05）. [ Concluslon~ The growth performance and apparent ileal digestibility of amino acids in broilers were increased with the rising supplementation of coated methionine, but the supplementation of 0.19% coated methionine can meet the needs of broilers, namely, coated methionine can be substituted for 60% DL-methionine in the diet, so DL-methio- nine can be saved up to 40%.

[D-Pen^2,D-Pen^5]enkephalin及Nor-binaltorphimine对吗啡损害小鼠自主选择能力的影响

选择性δ阿片受体激动剂[D-Pen^2,D-Pen^5]enkephalin(DPDPE),k阿片受体拮抗剂nor-bindtorphimine(N-BNI)在测试剂量下对小鼠在丫形迷宫中的自主选择能力无明显影响,但均可显著增强吗啡损害小鼠自主选择能力的作用。DPDPE对吗啡的协同作用还可被δ阿片受体拮抗剂ndltrindole(NTI)所拮抗。