Met-enkephalin Concentrations Research Articles

Measurement of substance P and met-enkephalin in the serum of violent death victims.

Very often the allocation of putative damages for wrongful death and the determination of aggravating factors in the sentencing of an individual convicted of homicide by a jury is based on a subjective determination of the amount of pain suffered by the victim. This study was designed to determine whether the quantitative determination of peptides involved in nociception and inflammation offer the potential to provide an objective basis for an assessment of pain prior to death. Two peptides. substance P and met-enkephalin, were quantitated using radioimmunoassay (RIA) in the serum of 131 autopsy subjects. Cases were selected that presented decedents who underwent a violent death resulting in extensive trauma to tissue. Only decedents with no known prior clinical manifestation and no indication of prior drug use were selected. Of 131 cases selected, 59 died from blunt trauma deaths, 47 from gunshot deaths, and 25 from stabbing deaths. Cases were selected without regard to whether the death was accidental, or by homicide or suicide. Values from cases having similar incident-death time intervals were pooled and then compared. Results show that an observable pattern exists between the concentrations of substance P and met-enkephalin and the incident-death time interval. Data showed that the concentrations of substance P and met-enkephalin vary with the incident-death time interval. The amount of serum substance P initially increases with increasing incident-death time interval but begins to decrease at longer incident-death time intervals. In contrast, the serum concentration of met-enkephalin continues to show increased concentration as the incident-death time intervals become greater. The Kruskal-Wallis test was performed to determine the level of significance of the variation in both peptide concentrations within four consecutive time intervals. Variation in substance P concentration was statistically significant in all comparisons performed with 0.01 being the lowest level of significance of any four consecutive groups tested. Conversely, intervals encompassing incident-death time intervals of 1-2 hours to 5-10 days did not demonstrate significant variation in met-enkephalin concentration. However, groups with smaller and larger time intervals than the nonsignificant groups did show statistical variation. Although owing to a number of variables, a direct correlation between peptide concentrations and the level of pain may not be possible, the results of the study indicate that a presumption of antemortem pain may be possible with future study.

A new electrochemical HPLC method for analysis of enkephalins and endomorphins

Endogenous opioid peptides, enkephalins and endomorphins, are located in key regions involved in pain transmission and analgesia, including the spinal cord. These endogenous peptides activate opioid receptors to produce analgesia and reduce pain. We describe a new method to measure enkephalin and endomorphins by high performance liquid chromatography with electrochemical detection. This method allows use of a small sample volume to measure met-enkephalin, leu-enkephalin, endomorphin-1 and endomorphin-2 simultaneously. Using push–pull perfusion of the spinal cord, there were detectable concentrations of met-enkephalin, leu-enkephalin, and endomorphin-2. Further infusion of 100 mM potassium chloride evoked release of met-enkephalin and endomorphin-2 but not leu-enkephalin. Thus, we have developed a method to simultaneously measure enkephalins and endomorphins in small sample volume that allows measurement of these opioid peptides in vivo.

Relative contribution of endogenous opioids to myocardial ischemic tolerance 1

Background Opioid preconditioning by exogenous opioids experimentally protects the myocardium against ischemia/reflow injury. Additionally, endogenous opioid peptides released during ischemia also enhance ischemic tolerance. Promiscuous opioid receptor agonists conceal the differential contribution of the mu (μ), delta (δ), and kappa (κ) opioid subtypes. This study compared the impact of selective δ and κ opioid receptor antagonists on postischemic functional and metabolic recovery. Also measured were changing levels of peptides dynorphin B and met-enkephalin during ischemia/reflow injury. Materials and methods Using the rabbit Langendorff model, the functional recovery of control hearts (following 2 h of global ischemia) was compared to hearts pretreated with δ antagonist NTB (1 μ m) or κ antagonist, nor-BNI (1 μ m). Measures included percentage of return of isovolumetric developed pressure (LVDP), myocardial oxygen consumption (MVO 2) and coronary flow (CF). In additional studies, untreated hearts were harvested at baseline, following ischemia, or following 5 or 45 min of reflow. Tissue concentrations of met-enkephalin and dynorphin B were measured by RIA. Results After 45 min of reflow, hearts pretreated with either NTB or nor-BNI showed impaired functional recovery by a decrease in LVDP ( P < 0.05); however, MVO 2 or CF were unaffected. RIA data shows that baseline levels of both peptides are similar and increase significantly during ischemia, but reflow dynorphin levels drop far below baseline, while met-enkephalin returns to baseline. Conclusion Antagonism of both δ and κ opioid receptor subtypes equally contributes to impaired left ventricular function, independent of altered perfusion or metabolic rate. Endogenous κ-receptor agonists may contribute primarily during ischemia or early reflow, since low late reflow dynorphin content did not correlate with altered functional recovery.

Chronobiology and anesthesia.

CHRONOBIOLOGY investigates biologic rhythms that are involved in the organization of living organisms. Biologic rhythms consist of variations of biologic phenomena that are periodic and foreseeable in time. They are genetically determined as indicated by their persistence during constant conditions such as continuous light or darkness. Temporal variations in cycles of light– dark, rest–activity, fasting–eating, and other environmental conditions, defined as synchronizers, give the organism temporal markers and thus impose their period on these biologic rhythms. These rhythms can therefore be characterized by different periods, leading to the division of circadian (a period of approximately 24 h), ultradian (a cycle that is shorter than 1 day), and infradian (a cycle that may last weeks, months, or seasons). These clocks influence how our bodies change throughout the day, affecting blood pressure, activity of the immune system, blood coagulation, and gastric and renal functions. Almost all hormones are regulated by circadian rhythms. For example, cortisol naturally decreases to its lowest concentrations at bedtime and reaches its highest concentrations during the early waking hours. This variation may be fit to a sinusoidal function by the cosinor method, a linear method of least squares (fig. 1). This function is characterized by parameters such as the midline-estimating statistic of rhythm (MESOR), i.e., the mean level that is equal to the 24-h average), amplitude (half of the peak-to-trough difference of the fitted cosinus function), and acrophase (the crest time of rhythm given in degrees, where 360° corresponds to a 24-h cycle, or in hours and minutes). Other methods, such as Fourier transformation, may be used to detect the periodicity of the rhythm. Biologic rhythms are influenced by socioecologic factors, such as jet lag and shiftwork, as well as by illness and drugs. Available clinical data have shown that signs and symptoms are not constant over time and often have cyclic patterns. More strokes and heart attacks occur in the morning compared with any other time of day, and people with osteoarthritis tend to feel less pain in the morning than at night. Studies also suggest that chemotherapy and treatments for asthma and arthritis may be more effective and less toxic if drugs are administered at carefully selected times. Taking into account the circadian rhythms for medical treatment by choosing the time of day for drug administration is called chronotherapy. Drug effects can be optimized and side effects can be reduced by basing drug administration on the circadian patterns of a disease. Chronopharmacology is the study of the influence of the moment of administration of a drug (hour, month, and year) on its response according to the temporal structure of the organism receiving it. Chronopharmacology also studies the drug-induced alterations of biologic rhythms. Two aspects of chronopharmacology must be distinguished: the time of administration of a drug may determine a different response from a qualitative or a quantitative point of view (chronopharmacodynamics) and/or a different effective drug concentration (chronopharmacokinetics). Pharmacokinetic parameters are influenced by different physiologic functions displaying circadian rhythm. Temporal changes of drug kinetics have been reported in animals and humans for more than a hundred drugs, including anesthetics. It has been shown, for example, that despite a constant infusion rate of heparin, the risk of bleeding and the activated partial thromboplastin are higher at night. Chronopharmacokinetic data may partly explain chronopharmacodynamic phenomena. Knowledge of the influence of the time of administration on the drug kinetics could therefore have implications for its prescription by modulating the distribution of the total daily dose over a 24-h period. The aim of this review is to provide an update on the chronobiologic and chronopharmacologic findings that could have an impact on the daily practice of anesthesiology and/or research in this area.

Dopaminergic system modulation of nociceptive response in long-term diabetic rats.

The present study examines the effects of dopaminergic system modulation on nociceptive response time in male diabetic rats. In this study, diabetes was induced by streptozotocin (STZ, 45 mg/kg) in adult male Sprague-Dawley rats. Insulin replacement therapy was initiated 6 weeks after the induction of diabetes for one-half of the diabetic group (1.5-2.5 IU/12 h/rat) and was continued throughout the duration of the study (up to 14 weeks). After 6 weeks of daily insulin replacement therapy, eight rats from each experimental group (STZ-diabetic, STZ-diabetic+insulin and nondiabetic control) were injected with either bromocriptine (BROM, 3 mg/kg/12 h), haloperidol (HALO, 1.5 mg/kg/12 h) or vehicle. Nociceptive response was measured by the hot plate (HP) latency test before the induction of diabetes (baseline), every 3 weeks for the first 12 weeks and then on days 5, 9 and 14 of treatment with dopaminergic agents. Animals were sacrificed 3 or 4 days after the last HP test and the brain, blood, spinal cord (SC), pituitary and adrenal glands (AD) were dissected for Met-enkephalin (ME) assay. The results show that nociceptive response of untreated diabetic animals increased gradually and significantly over the duration of this study. Administration of BROM and HALO significantly decreased and increased the nociceptive response, respectively, in all groups. However, the response of the diabetic group was more pronounced than that of the other two groups, especially for those treated with BROM. Daily insulin administration normalized nociceptive response to that of the nondiabetic controls. Diabetic animals receiving insulin replacement+BROM also showed normalized nociceptive response while the diabetic animals+HALO did not. Moreover, the administration of HALO and BROM resulted in an increase and decrease ME concentrations, respectively, in most tissues and brain regions examined. The effect of these dopaminergic agents on ME levels was greater in brain regions and tissues of the diabetic rats than in the diabetic groups receiving vehicle or in the nondiabetic control receiving these two agents. These data suggest that diabetes alters the sensitivity of the dopaminergic receptors and that altered response of the dopaminergic system could be indirectly involved in the modulation of nociception in diabetic rats possibly through the enhancement and/or deactivation of the endogenous Met-enkephalinergic system.

Met-enkephalin and preproenkephalin mRNA changes in the striatum of the nicotine abstinence mouse

We studied the changes of met-enkephalin (Met-Enk) content and preproenkephalin (PPE) mRNA in the striatum in a mouse model of nicotine abstinence. Nicotine, 2 mg/kg, s.c., was administered four times daily for 14 days and Met-Enk and PPE mRNA evaluated at various times (4–96 h) following drug discontinuation. Met-Enk, assayed by radioimmunoassay, was increased in the ventral (nucleus accumbens) but not dorsal (putamen/caudate) striatum, while PPE mRNA, assayed in whole striatum by Northern blotting was elevated. Both changes were seen early during withdrawal and lasted over 72 h. In situ hybridization revealed enhanced signal in the dorsal striatum, mostly laterally, and smaller increases in the rostral pole, core and shell of the nucleus accumbens. These observations indicate that during nicotine withdrawal, striatal enkephalinergic neurons undergo adaptative responses, which might contribute to the abstinence behavioral syndrome.

Is positive correlation between cortisol and met-enkephalin concentration in blood of women with breast cancer a reaction to stress before chemotherapy administration?

The role of stress in the course of neoplastic diseases has been emphasised over the past few years. Organism defence in form of increased release of hormones, corticosteroids and endogenous opioids should be assessed as a particular form of adaptation. Interactions between stress hormones and others which may influence the growth of breast cancer cells are possible. In this study, the concentration of cortisol and met-enkephalin vis-à-vis growth hormone, insulin-like growth factor-I, prolactin, estradiol, progesterone and melatonin in blood of women with breast cancer before the first cycle of supplementary chemotherapy was compared to that of healthy women. In a group of patients with breast cancer, before the first cycle of chemotherapy, high hypercortisolemia and positive correlation between cortisol and met-enkephalin was observed which may be a result of stress at the beginning of such treatment. A negative correlation between prolactin and met-enkephalin in this group can indirectly testify to essential participation of endogenous opioids in hormonal regulation and can be a response to stress caused by beginning chemotherapy.

Met‐Enkephalin Involvement in Morphine‐Modulated Peritonitis in Swiss Mice

Morphine coinjection with zymosan inhibits pain and leukocyte accumulation during peritonitis in several strains of mice, and affects systems of endogenous opioids. Present investigations focus on Met-enkephalin (Met-ENK) in the inflamed peritoneal cavity and brain centers of Swiss mice. Males of Swiss mice were IP injected with zymosan or zymosan supplemented with morphine. At the selected time points the peritoneal leukocytes were counted and the Met-ENK level was measured in exudatory fluid and leukocytes, striatum, hypothalamus, and pituitary gland. The Met-ENK content in peritoneal fluid rised sharply after zymosan injection, which corresponded with its decline in exudatory leukocytes, hypothalamus, and striatum. Morphine coinjection enhanced intraperitoneal accumulation of Met-ENK and its release from exudatory leukocytes, but inhibited its early fluctuations in hypothalamus and striatum. Effects of morphine-modulated inflammation on the Met-ENK system lasted longer than 7 days.

Mu-opioid receptor modulation of calcium channel current in periaqueductal grey neurons from C57B16/J mice and mutant mice lacking MOR-1.

1. The actions of opioid receptor agonists on the calcium channel currents (IBa) of acutely dissociated periaqueductal grey (PAG) neurons from C57B16/J mice and mutant mice lacking the first exon of the mu-opioid receptor (MOR-1) were examined using whole cell patch clamp techniques. These effects were compared with the GABA(B)-receptor agonist baclofen. 2. The endogenous opioid agonist methionine-enkephalin (met-enkephalin, pEC50 6.8, maximum inhibition 40%), the putative endogenous mu-opioid agonist endomorphin-1 (pEC50 6.2, maximum inhibition 35%) and the mu-opioid selective agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin, pEC50 6.9, maximum inhibition 40%) inhibited IBa in 70% of mouse PAG neurons. The inhibition of IBa by each agonist was completely prevented by the mu-receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2). The delta-opioid receptor agonists DPDPE ([D-Pen2,5]enkephalin, 1 microM) and deltorphin II (1 microM), and the kappa-opioid receptor agonist U-69593 (1-10 microM), did not affect IBa in any cell tested. 3. The GABA(B) agonist baclofen inhibited IBa in all neurons (pEC50 5.9, maximum inhibition 42%). 4. In neurons from the MOR-1 deficient mice, the mu-opioid agonists met-enkephalin, DAMGO and endomorphin-1 did not inhibit IBa, whilst baclofen inhibited IBa in a manner indistinguishable from wild type mice. 5. A maximally effective concentration of endomorphin-1 (30 microM) partially (19%), but significantly (P<0.005), occluded the inhibition of IBa normally elicited by a maximally effective concentration of met-enkephalin (10 microM). 6. This study indicates that mu-opioid receptors, but not delta- or kappa-opioid receptors, modulate somatic calcium channel currents in mouse PAG neurons. The putative endogenous mu-agonist, endomorphin-1, was a partial agonist in mouse PAG neurons.

Priming effect of met-enkephalin and β-endorphin on chemiluminescence, chemotaxis and CD11b molecule expression on human neutrophils in vitro

The opioid peptides are widely distributed throughout the body, and they are generated during stress and inflammatory reaction. Opioids are involved in the communication between the immune and neuroendocrine systems. In the present study we have investigated the ability of both met-enkephalin and β-endorphin to stimulate and prime the human neutrophils for enhanced chemiluminescence (CL) and chemotaxis induced with fMLP, OZ or PMA. We have also tested the affect of β-endorphin and met-enkephalin on CD11a, CD11b, CD18 and CD16 molecule expression on PMN in vitro. PMN from ten healthy donors were incubated in vitro with different concentrations of β-endorphin or met-enkephalin, and the CL response was evaluated with luminometer. To assess the effect of opioid peptides on CD11a, CD11b, CD18 and CD16 molecule expression the whole blood samples were incubated with different concentrations of the opioids, then the white cells were labelled with respective PE-conjugated MoAb and evaluated by flow cytometry. We have shown that: (1) met-enkephalin and β-endorphin at physiological concentrations relevant to that of in vivo (10 −8 and 10 −6 M) enhanced fMLP, PMA or OZ stimulated chemiluminescence and induced chemotactic response, (2) High concentrations of β-endorphin (10 −3 M) or met-enkephalin (10 −5 M) decreased the CL response of PMN in vitro, (3) The opioid peptides at lower concentrations resulted in CD11b and CD18 molecule up-regulation on neutrophils. We may conclude that opioid peptides in physiological concentration are involved in neutrophil priming whereas in higher concentration exert immunosuppressive potency. Opioid peptides like inflammatory cytokines may prime the neutrophils inflammatory response.

Hormonal changes during parturition in heifers and goats are related to the phases and severity of labour.

Parturition is a natural event that involves stress and pain for the mother. We thus hypothesized that levels of stress hormones measured during parturition could reflect levels reached in response to severe discomfort and pain of other kinds as well. The aim of this study was therefore to determine whether plasma concentrations of cortisol, adrenaline, noradrenaline, beta-endorphin, met-enkephalin, vasopressin and oxytocin vary depending on the phase and severity of labour in dairy heifers (ten) and dairy goats (six), and how these hormones interact with each other. Blood samples were taken once a day for 3 days before labour and for 3 days afterwards and at predetermined phases during labour. All heifers delivered one calf and five of them needed obstetrical assistance. Two of the goats delivered one kid, and four had twins; all kidded without help. The cortisol concentration peaked when the calf and the first kid were born. In the heifers, plasma adrenaline increased after delivery, while the noradrenaline concentration did not change significantly in heifers that needed assistance, but increased during expulsion in heifers calving without help. In the goats, adrenaline and noradrenaline concentrations increased in association with expulsion of the first kid. The beta-endorphin concentration increased during labour in goats. In heifers that needed assistance, beta-endorphin concentration increased 1 h after labour but there was no change in heifers that did not need assistance. The met-enkephalin concentration was elevated during expulsion in heifers and fluctuated in the goats. Both oxytocin and vasopressin increased during expulsion in both groups of heifers, but vasopressin increased four times more in heifers needing assistance. In the goats, oxytocin reached its highest levels just as the feet of the first kid became visible, and vasopressin peaked as the head emerged. Parturition took longer in heifers that needed assistance than in those that did not. It is concluded that, even though the pattern of change differed between hormones during labour, the changes were related to the phases of labour. A longer labour therefore meant that the hormone concentrations stayed elevated for longer. Vasopressin reached high levels in goats and was the only hormone for which plasma concentrations were higher in heifers that needed assistance than in those that did not, indicating that this hormone is released in order to deal with the pain-related stress associated with labour.

The enkephalinergic osteoblast.

The enkephalinergic osteoblast.

Enkephalin, PPE mRNA, and PTS-1 in alcohol withdrawal seizure-prone and -resistant mice

Inbred animal strains provide an opportunity to study genetic factors in alcoholism in the absence of environmental factors. Although the concentration of methionine enkephalin (Met-enkephalin) in whole brain has been implicated in the consumption of ethanol, it has not been studied in the brains of alcohol withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice. We compared these concentrations with the levels of preproenkephalin (PPE) mRNA and with the activity of peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin that is affected by ethanol. The concentrations of Met-enkephalin were significantly greater in WSP mice than in WSR mice, whereas synthesis of Met-enkephalin, as reflected by PPE mRNA levels, and transport out of the brain by PTS-1 was not different. These results support a direct link between elevated concentrations of Met-enkephalin in whole brain and proneness to withdrawal-induced seizures. We suggest that the inverse relationship between the consumption of ethanol and proneness to seizures in inbred mice can be explaimed through their opposite relationships to Met-enkephalin.

Monitoring of met-enkephalin in vivo with 5-min temporal resolution using microdialysis sampling and capillary liquid chromatography with electrochemical detection

A method based on microdialysis sampling and capillary liquid chromatography with electrochemical detection that allows in vivo monitoring of met-enkephalin with 5-min temporal resolution is described. Sampling was achieved using a concentric microdialysis probe made from polycarbonate membrane material with a 20 kDa cut-off. This probe had an in vitro relative recovery for met-enkephalin of 63% at a dialysis flow-rate of 0.6 μl/min. Separations were performed using 7 cm×25 μm I.D. fused-silica capillary columns packed with 5 μm Alltima C 18 particles. A carbon fiber microelectrode was used as the detector electrode. The mass detection limit for met-enkephalin with this system was 40 amol. With on-column preconcentration, up to 2 μl of sample could be loaded onto the column resulting in concentration detection limits as low as 20 p M for met-enkephalin. Direct injection of dialysate, collected at 5-min intervals, allowed determination of met-enkephalin concentrations in the rat globus pallidus under basal and K +-induced depolarization conditions.

Met-enkephalin alteration in the rat during chronic injection of morphine and/or midazolam

We have recently reported that the short-acting anesthetic and analgesic drug midazolam can produce analgesia and decrease morphine tolerance and dependence in the rat by interacting with the opioid system. This study was designed to investigate the effect of midazolam, morphine, and both together on met-enkephalin levels in the rat. Male Sprague–Dawley rats were divided into four groups: (1) saline-saline; (2) saline-morphine; (3) midazolam-saline, and (4) midazolam-morphine groups. First, a saline or midazolam injection was given intraperitoneally and after 30 min a second injection of saline or morphine was given subcutaneously once daily for 11 days. Animals were sacrificed on the 11th day 60 min after the last injection to measure met-enkephalin by radioimmunoassay. Morphine tolerant animals showed a significant increase in met-enkephalin levels in the cortex (137%) and midbrain (89%), and a significant decrease in met-enkephalin levels in the pituitary (74%), cerebellum (34%) and medulla (72%). Midazolam treated animals showed a significant decrease in met-enkephalin levels in the pituitary (63%), cortex (39%), medulla (58%), kidneys (36%), heart (36%) and adrenals (43%), and a significant increase in met-enkephalin levels in the striatum (54%) and pons (51%). When morphine and midazolam were injected together, midazolam antagonized the increase in met-enkephalin levels in cortex and midbrain region and the decrease in met-enkephalin level in the medulla region observed in morphine tolerant animals. These results indicate that morphine tolerance and dependence is associated with changes in the concentration of met-enkephalin in the brain. Midazolam may inhibit morphine tolerance and dependence by reversing some of the changes induced in met-enkephalin levels in brain by morphine in morphine tolerant and dependent animals.

Effect of preliminary adaptation to transauricular electrostimulation on the content of catecholamines and met-enkephalin in rat heart and adrenals in stress and acute myocardial infarction

Adaptation to transauricular electrostimulation decreases the content of epinephrine in the adrenal glands and norepinephrine in the heart. Immobilization stress has no appreciable effect on the content of catecholamines in the heart and adrenal glands. In animals with myocardial infarction, the content of norepinephrine in the heart decreases 2-fold, while the content of epinephrine in the adrenals decreases inconsiderably. Adaptation to transauricular electrostimulation is associated with a rise in met-enkephalin concentration. Preadaptation induces a more pronounced rise of met-enkephalin and promotes normalization of epinephrine in the adrenals, without changing the content of norepinephrine in the heart.

T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells

We investigated the regulatory influence of several cytokines on the expression of preproenkephalin (PPE) mRNA in human peripheral blood mononuclear cells (PBMC). By use of a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), we demonstrate that the T helper 2 cytokines IL-4 and IL-10 are more potent in upregulating PPE mRNA expression in human PBMC than the T helper 1 cytokines IL-2 and γ-IFN. In addition, TGF- β is also an effective inducer of PPE mRNA. TGF- β, IL-4 and IL-10 increase the cytoplasmatic concentration of met-enkephalin in PBMC. Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated. IL-4 and IL-10 do not induce PPE mRNA via the same pathways. We could observe that PKA is involved in IL-4 mediated PPE mRNA induction, whereas IL-10 apparently uses another route.

Ethanol alters the concentration of Met-enkephalin in brain by affecting peptide transport system-1 independent of preproenkephalin mRNA

Alcohol-related events have been proposed to be under neurochemical control. For example, the concentration of methionine enkephalin (Met-enkephalin) in brain has been inversely correlated with ethanol consumption in alcohol-preferring and alcohol-nonpreferring mice. The concentrations of Met-enkephalin are controlled in part by peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin located at the blood-brain barrier. We examined the relationships among concentrations of Met-enkephalin, preproenkephalin (PPE) mRNA, and PTS-1 activity in mice exposed to ethanol. PTS-1 activity decreased progressively during the process of addiction and then partially recovered within hours after withdrawal of ethanol. Serotonin lost its ability to modulate PTS-1 activity in exposed mice, indicating that regulation of PTS-1 activity was affected by ethanol. Concentrations of Met-enkephalin tended to move in the opposite direction from PTS-1 activity, increasing significantly with addiction. In naive mice, PPE mRNA levels correlated with the concentrations of Met-enkephalin. However, levels of PPE mRNA remained unchanged during addiction, withdrawal, and recovery, no longer correlating with concentrations of Met-enkephalin. These results suggest that ethanol affects concentrations of Met-enkephalin in brain through post-transcriptional mechanisms and that PTS-1 activity is one of those mechanisms.

Changes in the content of Met-enkephalin in different brain structures during the development of immune response

Changes in the content of the opiate peptide Met-enkephalin at the early stages of immune response are studied in different structures of rats brain 20 min and 24 h after immunization with sheep erythrocytes.

Is fatigue associated with cholestasis mediated by altered central neurotransmission?

Is fatigue associated with cholestasis mediated by altered central neurotransmission?