No abstract available.
Animals ; Dynorphins* ; Enkephalins* ; Prosencephalon* ; Rats* ; RNA, Messenger*

Humans ; Dynorphins/metabolism* ; Receptors, Opioid, kappa/metabolism* ; Cryoelectron Microscopy

PURPOSE: In mesial temporal lobe epilepsy (TLE). Hippocampl sclerosis (HS) is a pathologic substrate and characterized by significant neuronal loss and band-like synaptic reorganization in dentate inner molecular layer (DGIML) og sclerotic hippocampus with either Timm`s staining or Dynorphin (Dyn)-immunohistochemical staining methods. Hippocampus has neuronal synaptic circuitries of both intralamellar and translamellar patterns, from which we may hypothesize that longitudinal extent of HS represents variable pathophysiologic implications of neuronal injury, ictogenesis and epileptogenesis in mesial TLE. We tested the hypothesis. METHODS: Eleven mesial TLE patients with HS on MRI were recruited from epilepsy surgery registry. Resected hippocampal slices were stained with Dyn immunohistochemical method. We classified them into cases with partial HS and thoes with extensive HS according to longitudinal HS extent,. Between the two groups, clinical characteristics of seizures or epilepaies, Hippocampal neuronal density and neuronal loss. and Dynimmunoreactivity (IR) patterns were compared and analyzed. Dyn-IR pattern was classified as presence or absence of DGIML band and of CA3-IR. RESULTS: Nine cases showed extensive HS whereas two were classified as partial HS. There appeared no significant differences in clinical characteristics, neuronal density, neuronal loss and Dyn-IR patterns between those with extensive and partial HS. CONCLUSION: In this study, we could not prove the hypothesis that difference in HS extend on MRI may represent distinctive variabliity in severity of hippocampal neuronal injury and in ictiogenetic or epileptogenetic pathophysiology.
Dynorphins ; Epilepsy ; Epilepsy, Temporal Lobe* ; Hippocampus ; Humans ; Magnetic Resonance Imaging ; Neurons* ; Sclerosis* ; Seizures ; Temporal Lobe*

Animals ; Dynorphins ; metabolism ; Parkinson Disease ; drug therapy ; metabolism ; Peptides ; pharmacology ; Rats ; Scorpion Venoms ; pharmacology

DREAM (downstream regulatory element antagonistic modulator) is a calcium-binding protein that regulates dynorphin expression, promotes potassium channel surface expression, and enhances presenilin processing in an expression level-dependent manner. However, no molecular mechanism has yet explained how protein levels of DREAM are regulated. Here we identified group I mGluR (mGluR1/5) as a positive regulator of DREAM protein expression. Overexpression of mGluR1/5 increased the cellular level of DREAM. Up-regulation of DREAM resulted in increased DREAM protein in both the nucleus and cytoplasm, where the protein acts as a transcriptional repressor and a modulator of its interacting proteins, respectively. DHPG (3,5-dihydroxyphenylglycine), a group I mGluR agonist, also up-regulated DREAM expression in cortical neurons. These results suggest that group I mGluR is the first identified receptor that may regulate DREAM activity in neurons.
Calcium ; Cytoplasm ; Dynorphins ; Methoxyhydroxyphenylglycol ; Neurons ; Potassium Channels ; Presenilins ; Proteins ; Receptors, Metabotropic Glutamate ; Up-Regulation

BACKGROUND: We studied the time course of gene expression of dynorphin, enkephalin, c-fos, and the changes of allodynia, and the effect of chemical sympathectomy on the gene expression and allodynia in neuropathic rat. METHODS: In two groups of rat (Sprague-Dawley), the left L5 and L6 spinal nerves were tight ligated. In gene expression group (N=25), behavioral tests for mechanical allodynia and cold allodynia were perfomed for the next two weeks. After the test of allodynia, the expression of dynorphin, enkephalin, c-fos were assessed by Northern blot hybridization. In chemical sympathectomy group (N=16), after chemical sympathectomy (guanethidine 70 mg/kg intraperitoneally, from postoperative 7 days to 9 days), the changes of allodynia and the gene expression of enkephalin, c-fos were tested. RESULTS: Mechanical allodynia and cold allodynia was developed on the postoperative 3, 5, 7, 14 days. Preprodynorphin mRNA expression was reached peak level at the postoperative 8 hrs, sustained increase by the postoperative 3 days, but preproenkephalin mRNA expression increased slightly after operation. c-Fos mRNA expression was increased immediately at the postoperative 30 min, 1 hr, returned to normal level thereafter, and increased again on the postoperative 3, 5, 7 days that neuropathic pain was developed. Mechanical allodynia and cold allodynia were decreased by chemical sympathectomy. The increased c-fos mRNA expression and pain at postoperative 7 days was reduced by chemical sympathectomy. CONCLUSION: These results suggest that the transient gene expression of dynorphin and c-fos after tight ligation of L5 and L6 spinal nerves induces the development neuropathic pain, and late c-fos expression is related to neuropathic pain.
Animals ; Blotting, Northern ; Dynorphins* ; Enkephalins* ; Gene Expression* ; Hyperalgesia ; Ligation ; Neuralgia ; Rats* ; RNA, Messenger ; Spinal Nerves ; Sympathectomy, Chemical

BACKGROUND: Dynorphin A (1-17) is conceived as an endogenous opioid peptide with a high degree of selectivity forkappa- opioid receptor even though it has been reported to sometimes act like amicro- opioid agonist. The aim of this study was to investigate [35S] GTPgammaS binding stimulated activation by dynorphin A (1-17) in the cerebral and thalamic membranes of a rhesus monkey. METHODS: The rhesus monkey (Macaca mulatta, male, n = 1) was euthanized for the preparation of the cerebral and thalamic membranes. Protein concentrations were determined by the Bradford method. In the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve, EC50 (effective concentration 50 nM) and maximum stimulation (% over basal) were determined in the absence or presence of themicro-andkappa-opioid receptor antagonists naloxone (20 nM) and norbinaltorphimine (nor-BNI, 3 nM), respectively. E2078-stimulated [35S] GTPgammaS binding was also determined in the absence or presence ofmicro-andkappa-opioid receptor antagonists in the cortical membrane and compared with dynorphin A (1-17). RESULTS: Values of EC50 and maximum stimulation of dynorphin A (1-17)-stimulated [35S] GTPgammaS binding were as follows: cortex (474 nM/32.0%) and thalamus (423 nM/45.3%). Nor-BNI (3 nM) did not antagonize dynorphin A (1-17)-stimulated [35S] GTPgammaS binding at all in cortical or thalamic membrane, but naloxone (20 nM) produced a 12.2 fold rightward shift of the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve in the thalamic membrane. The EC50 and the maximum stimulation of E2078-stimulated [35S] GTPgammaS binding were 65.6 nM and 22.7%, respectively. In E2078-stimulated [35S] GTPgammaS binding, the dose-response curve was antagonized not by nor-BNI but by naloxone but in the cortical membrane (a 14.2 times rightward shift). CONCLUSIONS: Dynorphin A (1-17) is selective formicro-opioid receptor in agonist-stimulated [35S] GTPgammaS binding in the cortical and thalamic membranes of rhesus monkey.
Dynorphins* ; Guanosine 5'-O-(3-Thiotriphosphate)* ; Haplorhini* ; Humans ; Macaca mulatta ; Male ; Membranes* ; Naloxone ; Opioid Peptides ; Receptors, Opioid ; Thalamus

In the rat hippocampal formation, the time-course and dose-response of the expression of enkephalin and dynorphin gene were examined after kainate (KA) treatment with in situ hybridization histochemistry. The KA induced enkephalin and dynorphin mRNA expression in hippocampus occurred mainly in the dentate gyrus. The enkephalin mRNA expression appeared at 3hour after KA injection, increased dramatically at 6hour, and then decreses. At 24hour after KA injection, the expression of enkephalin mRNA disappeared. The dynorphin mRNA expression appeared at once after injection and increased dramatically at 3hour. Unexpectedly at 6hour after injection, the expression was decreased, and then increased less than the 3hour expression. The increased pattern persisted to 24hour after injection. Unexpected result was also encounted in the experiment of KA dose-response of enkephalin mRNA and dynorphin mRNA. In the hippocampal formation, in contrast with other areas, low dosage (8mg/kg) of KA induced more significant expression of both genes than high dosage (16mg/kg) of KA.
Animals ; Dentate Gyrus ; Dynorphins ; Enkephalins ; Gene Expression* ; Hippocampus* ; In Situ Hybridization ; Kainic Acid ; Opioid Peptides* ; Rats* ; RNA, Messenger ; Seizures*

Septic shock is one of the leading cause of death in hospitalized patients and mortality rates of up to 50 % have been reported. Despite all efforts, no regimen today seems to be successful in the treatment of septic shock. The endogenous opioid system (EOS) includes three major families of peptides: dynorphins, endorphins and enkephalins. Several lines of evidence indicate that EOS is implicated in the pathophysiology of anaphylactic and endotoxic shock. An opioid receptor blocker naloxone has been used extensively in studies for the role of EOS or endogenous opiod peptides (EOP). However, there have been few, if any, detailed investigative studies regarding the effect of naloxone on TNF-a production and the lethality in response to endotoxin, and tumorigenesis. ...continue...
Carcinogenesis* ; Cause of Death ; Dynorphins ; Endorphins ; Enkephalins ; Humans ; Melanoma ; Mortality ; Naloxone* ; Nitric Oxide ; Peptides ; Receptors, Opioid* ; Shock, Septic*

Opiate receptor agonists (especially dynorphin - a kappa receptor agonist) have found to increase in the injuried segment of spinal cord. It is known to cause spinal cord damage when injected intrathecally. Nalbuphine is a kappa opiate receptor agonist/partial mu antagonist, and fentanyl is selective mu receptor agonist. To determine the effect of nalbuphine and fentanyl on experimental spinal cord injuries of Spague-Dawley rats (N=125): 1) I determinded the MAC (or ED50) values of enflurane, fentanyl, nalbuphine-enflurane in 65% N2O; 2) produced spinal cord injury model by different epidural ballooning time in the control (enflurane) gmup ; 3) produced spinal cord injuries in the experimental (fentanyl, nalbuphine-enflurane) group. The results were as follows ; 1) The MAC value of enflurane was 1.16+/-0.05%, and the ED50 values of fentanyl were 26.8, 36.2, 39.7, 44.7 ug/kg after 15, 30, 45, 60 min of injection, respectively. Also the MAC values of enflurane with 20 mg/kg nalbuphine were 1.08, 0.99% after 60, 90 min of injection, respectively. 2) We produced the graded spinal cord injuries by different epidural ballooning time. 3) The total neurological scores of fentanyl experimental group were significantly higher than control group on the 10th, 14th, and 21st postinjury day.
Animals ; Dynorphins ; Enflurane ; Fentanyl* ; Nalbuphine* ; Rats ; Receptors, Opioid ; Receptors, Opioid, kappa ; Receptors, Opioid, mu ; Spinal Cord Injuries* ; Spinal Cord*