Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “dipeptides”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed1985

Muramyl dipeptide and polymorphonuclear leukocyte chemotaxis in vitro.

Muramyl dipeptide (MDP) is an immunostimulatory agent that has been shown repeatedly to provide protection against the effects of some forms of experimental surgical infection. The mechanisms of this protection are incompletely understood, and in order to further define them, the impact of MDP upon in vitro polymorphonuclear (PMN) leukocyte chemotaxis was examined in the presence of both normal and opsonic depleted serum. We have also evaluated the effect of MDP as a chemoattractant itself and the response of neutrophils along with MDP to a standard chemoattractant, n-formyl-L-methionyl-L-leucyl-L-phenyl-alanine (FMLP), using the agarose assay for chemotaxis. MDP has weak but significant chemotactic activity itself, with a peak effect at a concentration of 5 X 10(-8) micrograms/ml for neutrophils. These effects are enhanced by the addition of 10% serum. MDP more strongly enhances neutrophil chemotaxis to FMLP. The enhancement of chemotaxis may be a factor in the protection that MDP exerts against some experimental bacterial challenges.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Effects of muramyl dipeptide and clindamycin in a murine abdominal abscess model.

Peritonitis and subsequent local and remote complications are an important source of morbidity and mortality, which persist despite the best available treatment. Reasonable therapeutic efforts, therefore, have included stimulation of host defenses with immune adjuvants, recently typified by muramyl dipeptide (MDP). Murine abdominal abscesses were created by intraperitoneal injection of Bacteroides fragilis and autoclaved fecal suspensions, and the effects of MDP and clindamycin on these abscesses were evaluated. At 10(4) colony-forming units (CFU) per milliliter of Bacteroides fragilis, intraperitoneal clindamycin was effective in reducing both the incidence of abscess formation as well as the number of abscesses per mouse as compared with controls at doses of 5 mg/kg and 2 mg/kg (P less than 0.01). The effect was more significant when the drug was given 30 min prior than when given after injection of organisms (P less than 0.02). At 10(7) and 10(8) CFU/ml, pretreatment with MDP increased abscess formation (P less than 0.05, P less than 0.01), an effect that was obscured by clindamycin administration, which decreased number of abscesses from controls irrespective of pretreatment with MDP. Abscesses were present on the third day after injection, and MDP, paradoxically, had increased the number of abscesses by the fifth day. Clindamycin reduced abscess formation at all concentrations of bacteria and had a dose and time-dependent response. MDP increased abscess formation only at high concentrations of Bacteroides fragilis, but clindamycin abolished this effect and reduced the number of abscesses to similar levels in both the clindamycin alone and clindamycin + MDP groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1990

Muramyl dipeptide improves mononuclear phagocyte system function in obstructive jaundice.

Previous studies have demonstrated depression of the mononuclear phagocyte system (MPS) of which the liver comprises 80-85% in animals subjected to 21 days of obstructive jaundice. This study examined the ability of a macrophage stimulant, muramyl dipeptide (MDP), to reverse MPS dysfunction in an obstructive jaundice rat model. Sixty-two male Sprague-Dawley rats underwent sham (n = 29) laparotomy or common duct ligation (CDL) (n = 33) and were studied after 21 days. Animals were injected with 1-3.5 X 10(6) Escherichia coli via a lateral tail vein, and colony-forming units (CFU) of the liver, lung, and spleen were determined at two time intervals: 30 min postinjection to determine the phagocytic activity of MPS (sham, n = 16; CDL, n = 20) and 24 hr postinjection to determine cytotoxic activity of MPS (sham, n = 13; CDL, n = 13). MDP (3 micrograms/g) was administered subcutaneously 24 hr prior to E. coli injection in 6 sham and 10 CDL rats studied at the 30-min time interval and 7 sham and 7 CDL rats studied at the 24-hr time interval. Pretreatment with MDP appeared to reverse the impairment of phagocytic activity in the liver of CDL rats returning it to the level of sham animals (P less than 0.05). However, pretreatment with MDP did not enhance the cytotoxic activity of the MPS as evidenced by higher CFU of E. coli in the liver, lung, and spleen of CDL animals pretreated with MDP as compared to CDL animals that did not receive MDP pretreatment. This increase was only significant in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Endogenous morphine and codeine in mice--effect of muramyl dipeptide.

Administration of morphine exerts many effects on the immune system. On the other hand little attention has been paid to the fact, that endogenous morphine and codeine exists in mammals, including man. This raises the question, whether or not endogenous opiate alkaloids play some role in immunoregulation. In addition muramyl-dipeptide (MDP), product of bacterial cell wall degradation and a potent immunomodulatory agent exhibits a broad spectrum of effects including effects on CNS functions. The present study investigated whether or not the endogenous levels of morphine and codeine are affected by administration of MDP in mice. Marked variation was found in spleen, brain, small intestine and heart in morphine and codeine concentrations. The intraperitoneal administration of MDP produced a significant increase in tissue morphine levels 30 minutes after injection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Muramyl dipeptide, amphetamine, and physostigmine: effects on sleep of rabbits.

Muramyl peptides (MPs) are constituents of bacterial cell walls and mammalian tissue. Some MPs have the capacity to enhance slow-wave sleep (SWS). In rabbits, it was unknown whether MPs enhanced SWS by prolonging SWS episodes or by increasing the number of SWS episodes. In rabbits, there is a frequent alternation between sleep and waking; thus, demonstration of induction of new SWS episodes is difficult unless pharmacologic manipulations are used. We injected amphetamine subcutaneously to reduce duration of sleep (from about 45% to 20%) for a period of two hours; it reduced the number of SWS episodes. Muramyl dipeptide (MDP: NAM-L-ala-D-isogln) injected into a lateral ventricle one hour before amphetamine significantly increased the number of SWS episodes. Physostigmine, a cholinergic agonist, was also used. By itself, physostigmine greatly reduced SWS and rapid eye movement sleep. Pretreatment of animals with MDP two hours before physostigmine injection failed to reverse subsequent physostigmine-induced wakefulness. We conclude that MDP has the ability to induce SWS episodes but does not act directly on the thalamocortical cholinergic mechanisms of EEG phenomena. Our results, together with earlier evidence on anatomical levels of action of amphetamine and physostigmine, suggest that the somnogenic mechanisms of MPs likely involve the midbrain.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Comparison of the effects of bacterial lipopolysaccharide and muramyl dipeptide on food intake.

For further characterization of the mechanism involved in the anorexia during bacterial infection, we investigated whether muramyl dipeptide (MDP), the minimal immunologically active structure of gram-positive bacterial cell walls, affects rats' food intake in the same way as lipopolysaccharide (LPS) from E. coli. MDP (1.6 mg/kg body weight = b.wt.) injected intraperitoneally (IP) reduced food intake by decreasing meal frequency without affecting meal size. Indomethacin (2.5 mg/kg b.wt., IP) but not verapamil (5 mg/kg b.wt., IP) attenuated the hypophagic effect of MDP. In further experiments, MDP and LPS (100 micrograms/kg b.wt., IP) both inhibited gastric emptying and indomethacin failed to block this effect of LPS. Hepatic vagotomy did not attenuate the hypophagic effects of MDP or LPS. LPS reduced water intake only when food was available, but reduced food intake also during water deprivation. MDP did not affect water intake. MDP and LPS both had an aversive effect, but LiCl, which was also aversive, failed to reduce feeding under the conditions tested. This questions the role of a conditioned taste aversion in the hypophagia induced by MDP or LPS. The results suggest that a stimulation of eicosanoid synthesis contributes to MDP-induced hypophagia and may therefore also contribute to the anorexia during infection. In contrast, an inhibition of gastric emptying, an activation of hepatic satiety signals or a reduction of water intake, does not seem to be crucial for the hypophagic effects of MDP or LPS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Activation of rainbow trout (Oncorhynchus mykiss) phagocytes by muramyl dipeptide.

Immunoenhancing activity of synthetic muramyl dipeptide (MDP) was investigated in relation to the activation of rainbow trout (Oncorhynchus mykiss) phagocytes and to nonspecific protection against challenge with the fish pathogen Aeromonas salmonicida. Head kidney phagocytes collected from MDP-injected fish showed significant chemotactic activity against zymosan-activated normal rainbow trout serum, and phagocytic activities against both A. salmonicida and plastic beads. The MDP-activated phagocytes also showed enhanced superoxide generation. When normal phagocytes were exposed to supernatants of phagocyte or peripheral blood lymphocyte cultures of MDP-injected fish, the cells showed significant chemotactic activity, indicating that the MDP-activated cells produced phagocyte-activating factor. Injection of MDP to fish provided protection against challenge with virulent A. salmonicida.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

The synthetic immunomodulator muramyl dipeptide (MDP) can stimulate activated B cells.

The synthetic immunomodulator muramyl dipeptide (MDP) has previously been shown to be able to synergize with lymphokines in enhancing the specific immune response of purified splenic B cells. Here, we have examined the effect of MDP in the process of B cell activation. We found that MDP alone was ineffective on the proliferation of either murine resting or in vivo activated B cells, whereas it enhanced the DNA synthesis of B cells once stimulated with anti-IgM antibodies. In agreement with these findings, cell cycle analysis by flow cytometry after acridine orange staining indicated that MDP by itself could not trigger the entry into the G1 phase of the cell cycle of nonactivated B lymphocytes. In contrast, in the presence of anti-IgM antibodies plus BSF-1, MDP promoted further cell cycle progression preferentially into the G1B compartment and also through the G2/M phase. A kinetic study showed that MDP was the most effective when added after the activation of B cells by anti-IgM antibodies plus BSF-1. Our present results suggest that functional receptors for MDP may be expressed on already cycling B cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Effects of treatment with muramyl dipeptide on resistance to Mycobacterium leprae and Mycobacterium marinum infection in mice.

Studies were carried out to determine whether treatment of mice with the synthetic adjuvant muramyl dipeptide (MDP) afforded resistance to infection with Mycobacterium leprae or M. marinum in mice. Regardless of the timing, dose, or route of administration, there was no evidence that treatment with MDP or 3 of its analogs (desMDP, abuMDP, valMDP) enhanced resistance to food pad infection with M. leprae or M. marinum. In parallel studies, systemic treatment with Propionibacterium acnes failed to protect against either M. leprae or M. marinum. Administration of P. acnes locally into the foot pad afforded marginal resistance to M. marinum when injected prior to infection. Local treatment with P. acnes afforded marked resistance to growth of M. leprae, even when administered months after infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Differences in interleukin 1 (IL-1), IL-6, tumor necrosis factor and IL-1 receptor antagonist production by human monocytes stimulated with muramyl dipeptide (MDP) and its stearoyl derivative, romurtide.

The immunostimulatory reagents muramyl dipeptide (MDP) and its stearoyl derivative romurtide [MDP-Lys(L18)] were assessed for cytokine inducing activity in human monocytes. Both MDP and romurtide stimulated the production of interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) and IL-1 receptor antagonist (IL-1Ra). Kinetics study indicated that IL-1, TNF and IL-1Ra were induced after 4 h stimulation but IL-6 was produced at a later phase. Romurtide induced these cytokines for longer period that MDP. Dose-response study indicated that romurtide was far more potent than MDP in induction of IL-1, IL-6 and TNF. Although the magnitude of the IL-1 and IL-6 induction was almost the same, that of TNF induction was greater in romurtide-stimulated monocytes than in MDP-stimulated cells. Among IL-1, IL-1 beta appeared to be a major product. In contrast to other cytokines, IL-1Ra was induced by MDP and romurtide in a similar dose and time dependent manner with similar magnitude of response. These studies indicate that MDP and romurtide, especially romurtide, are very potent inducers of both immunostimulatory and immunosuppressive cytokines by human monocytes but with different efficacy and kinetics.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). II. Use of compounds of the muramyl dipeptide (MDP) family as adjuvants.

Earlier tests of an antipregnancy vaccine consisting of the beta-subunit of human chorionic gonadotropin (beta-hCG) linked by reaction with a carbodiimide reagent to tetanus toxoid (TT) and adsorbed on Al(OH)3 resulted in antibody responses that were judged inadequate in some women. Experiments were therefore conducted to evaluate the effectiveness of additional adjuvants in increasing the antibody response. Muramyl dipeptide (MDP) and several of its analogs were formulated with the vaccine and tested in rabbits. Some of the analogs, and notably N-acetyl-normuramyl-L-alanyl-D-isoglutamine, elicited substantial increments in the ability of the antisera to bind [125I]hCG and in its ability to neutralize hCG in the rat uterine weight assay. The effectiveness of these peptides was greatest when formulated in a water-in-oil emulsion. Increments of 10 fold were attained using a vegetable oil as the oil component. The MDP analogs were much less effective as adjuvants when formulated in oil-in-water emulsions or in aqueous suspensions of the antigen. It is concluded that selected MDP analogs incorporated in a water-in-vegetable oil emulsion can markedly increase the circulating antibody response to the beta-hCG-TT vaccine.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Increased expression of alkaline phosphatase activity in stimulated B lymphocytes by muramyl dipeptide.

We have recently shown that the synthetic immunomodulator muramyl dipeptide (MDP) acts on murine B lymphocytes. It synergizes with interleukin 2 and interleukin 4 to stimulate, respectively, the differentiation and the proliferation of B cells. In the present study, MDP was shown to increase the proliferation of B cells stimulated by lipopolysaccharide (LPS). Moreover, the expression of alkaline phosphatase activity induced by LPS was markedly enhanced by MDP. These effects were time- and dose-dependent. The present report suggests that the biochemical mechanism by which MDP exerts its effects may involve protein phosphorylation-dephosphorylation pathways.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Differential regulation of surface immunoglobulin expression by various muramyl dipeptides in a murine pre-B cell line.

The murine pre-B cell line 70Z/3 responds to lipopolysaccharide (LPS), interleukin-1 (IL-1) or interferon-gamma (IGN gamma) by kappa gene transcription and expression of surface IgM (sIg). We found that muramyl dipeptide (MDP), a synthetic immunoadjuvant analog of a bacterial membrane structure, produced a weak increase in the number of sIg-positive 70Z/3 cells as measured by immunofluorescence staining. This number was significantly increased after exposure to MDP. Moreover, when MDP was used in combination with LPS, IL-1 or IFN gamma, an enhancement of sIg expression was observed showing an early influence of MDP in the presence of a second stimulant. Unexpectedly, two adjuvant-active analogs of MDP did not share its capacity to stimulate differentiation of the cell line when used alone or associated with other agents, indicating that adjuvanticity of MDP was not the only requirement. Two other products of bacterial origin, a Staphylococcus aureus cell extract (SAC) and the Toxic Shock Syndrome Toxin TSST-1 could neither enhance the kappa gene expression in 70Z/3 cells nor increase the MDP effect. The stimulating effect displayed by MDP could by related to NF-kappa B activation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

The occurrence of natural antibodies to minimal component of bacterial cell wall (N-acetylglucosaminyl-N-acetylmuramyl dipeptide) in sera from healthy humans.

ELISA assay showed that sera from each of 729 healthy donors contained antibodies to the minimal component of bacterial cell walls, N-acetylglucosaminyl-N-acetylmuramyl dipeptide (GMDP). Anti-GMDP antibody levels were determined for 686 sera which were classified into 3 groups: high (17.6%), medium (68.7%), and low responder (13.7%). Inhibition analysis performed on representative sera showed that a proportion contained specific anti-GMDP antibodies reacting only with GMDP (i.e., GMDP interaction with anti-GMDP antibodies was inhibited by GMDP only) whereas the remaining sera reacted both with GMDP and with the tetrasaccharide (GlcNAc-MurNAc)2 (i.e., GMDP interaction with anti-GMDP antibodies in the latter sera was inhibited by both GMDP and the tetrasaccharide). Inhibition analysis indicated, moreover, that the anti-GMDP antibodies contained in high-responder sera had higher affinity than those present in low-responder ones: GMDP inhibited the GMDP + anti-GMDP antibody interaction by 88.7% in the former sera vs. 53% in the latter. Sera contained both IgM and IgG antibodies to GDMP, but the mean level of anti-GMDP IgG antibodies in the high-responder sera was 30 times higher than in the low-responder ones.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Muramyl-dipeptide, a macrophage-derived cytokine, alters neuronal activity in hypothalamus and hippocampus but not in the dorsal raphe/periaqueductal gray of rats.

Muramyl-dipeptide (MDP) is derived in vivo by degradation of bacteria cell walls and is the minimum fragment that stimulates the acute phase response to bacterial infection. The present study investigates whether this specific product of an immune response affects central nervous system (CNS) function. To this end, the activity of single neurons within the hypothalamus, hippocampus, and dorsal raphe/periaqueductal gray region prior to and following systemic (i.p.) injection was studied. The results obtained from a total of 120 cells demonstrate that single hypothalamic and hippocampal neurons, sites previously shown to aid in the integration of various environmental stimuli into physiologic processes, alter their neuronal activity in site-specific manners following MDP administration. The specificity of the responses included both the threshold for activation of particular sites, effects of increasing dosages upon response pattern characteristics, and time course to the changes observed. These results therefore suggest that MDPs may play a role in the neuro-immunologic regulatory pathways during the immune response to bacterial infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Cloning and characterization of cDNAs for novel proteins with glutamic acid-proline dipeptide tandem repeats.

cDNAs with identical 3' sequences containing a hexanucleotide repeat -(GAGCCG)9- were isolated from rat pheochromocytoma and brain cDNA libraries. The cDNA with the longest open reading frame codes for a protein of 24.6 kDa containing a 16-fold -(Glu-Pro)- dipeptide repeat within a glutamate and proline rich region at its deduced C-terminus. cDNAs with the identical 3' sequence and a divergent 5' sequence were isolated from a rat skeletal muscle cDNA library. The latter are predicted to code for a protein of 15.5 kDa with a C-terminal repetitive domain identical to that in the pheochromocytoma and brain cDNAs. The cDNAs recognize a 1.8 kb mRNA species present in a variety of tissues, being particularly abundant in cardiac and skeletal muscle.

Amino Acid Sequence↗
PubMed1987

Interacting sleep-modulatory effects of simultaneously administered delta-sleep-inducing peptide, muramyl dipeptide and uridine in unrestrained rats.

A 10-h nocturnal intracerebroventricular infusion of 2 or 3 sleep substances such as 2.5 nmol delta-sleep-inducing peptide (DSIP), 2.0 nmol muramyl dipeptide (MDP) and 10 pmol uridine resulted in a significant, combination-dependent change in sleep-waking dynamics, which was quite different from the time-course sleep promotion induced by the single administration of each substance. The DSIP-MDP combination was characterized by a profound increase in SWS only at the middle infusion period. PS was little affected. The DSIP-uridine combination exerted a slight increase in SWS at the late infusion period with little change in PS parameters. The MDP-uridine combination caused a marked increase in both SWS and PS only at the early to middle infusion period. The DSIP-MDP-uridine combination induced an extremely large increase in SWS at the early to middle phase of the infusion period. PS significantly increased only at the early phase. These results may suggest that the sleep substances acted in tandem, either synergistically or antagonistically, on the sleep regulatory mechanism.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Fate of the synthetic immunoadjuvant, muramyl dipeptide (14C-labelled) in the mouse.

Synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide or MDP) represents the smallest unit that can substitute for whole Mycobacteria in Freund's complete adjuvant. In this paper the fate of 14C-labelled (on the muramyl moiety) MDP is reported. Following intravenous or subcutaneous injection into mice, more than 50% of 14C-MDP was recovered in the urine after 30 min and more than 90% after 2 h. The labelled compound was found unchanged in the urine, as shown by detailed analyses. However, MDP was sequestered for a longer time at the site of injection when administered as a water-in-oil emulsion. Considering the relatively rapid elimination observed, it is suggested that the biological effects of MDP and related compounds, when administered in an aqueous medium, may be due to their activity at minute concentrations and/or an immediate action at the cellular level.

Acetylmuramyl-Alanyl-Isoglutamine↗