Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated spaced injection of small amounts of beta-endorphin or Met-enkephalin into the hippocampus or posterior amygdala of the rat led to the development of kindled generalized convulsions. Similar injection of morphine into the hippocampus or anterior amygdala resulted in epileptiform spiking followed by tolerance. The epileptiform spiking and convulsive behavior varied in a dose-related manner. Naloxone blocked or greatly attenuated the electrographic seizure and convulsive behavior. Prior kindling with beta-endorphin or Met-enkephalin significantly facilitated electrical kindling of the amygdala. Handling or conspecific threat potentiated the epileptiform spiking and convulsive behavior in some cases. The results indicate that the epileptogenic response to intracerebrally applied opioid peptides is site-specific within the rat brain, and they support the idea that endogenous opioid mechanisms may play a role in convulsive seizures. They also suggest a possible opiate-based mechanism for the stress-induced exacerbation of seizures.
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PMID:Epileptiform effects of met-enkephalin, beta-endorphin and morphine: kindling of generalized seizures and potentiation of epileptiform effects by handling. 316 84

In a previous study we found depressed ACTH and normal beta-endorphin values in the cerebrospinal fluid of patients with West's syndrome, whereas normal peptide levels were present in infants with secondary Infantile spasms. This prompted us to study the effects of naloxone administration in children with West's syndrome. After informed consent was obtained from the parents, the effects of naloxone administration on clinical and EEG findings were evaluated in five infants 5-9 months old (3 males, 2 females) with cryptogenic infantile spasms and hypsarrhythmia. The infants were studied at the onset of symptomatology before therapy. An average of 5-10 groups of spasms were present per day. Naloxone (12 micrograms/kg body weight) was administered as an intravenous bolus in two cases, as a slow venous drip in another two cases, and intramuscularly in the last case. EEG and polygraphic monitoring were performed for 2 h. Naloxone did not induce any acute behavioral changes and the number of seizures remained unchanged after treatment. These data reject the possibility that endogenous opioids tonically modulate infantile spasms. Further studies are required to ascertain the involvement of POMC peptides in West's syndrome.
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PMID:Lack of clinical-EEG effects of naloxone injection on infantile spasms. 324 47

Pregnant mice are more susceptible to flurothyl-induced seizures than are non-pregnant controls. The possibility that the well-known increase in beta-endorphin concentration which accompanies pregnancy was involved in this effect was examined by testing whether naloxone administration could block the increased seizure susceptibility. Pregnant female, control female and male C3H mice were treated with 5-50 mg/kg naloxone 5 min before flurothyl seizure testing. Naloxone markedly increased clonic seizure susceptibility in all three groups at a dose of 50 mg/kg, but had little effect at lower doses. In contrast, naloxone had differential effects on myoclonic seizures in pregnant and control female mice, being anticonvulsant in the controls, but proconvulsant in the pregnant mice. A role for endogenous opiates is unlikely in mediating clonic seizures in pregnant mice, but may be involved in myoclonic seizures.
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PMID:The effect of naloxone administration on pregnancy-associated seizures. 371 30

The ability of the opiate peptides met-enkephalin and B-endorphin to kindle seizures, and for the opiate seizures to transfer to electrical kindling was examined in hooded rats using the direct injection of opiate into the brain. The injections resulted in a site-specific kindling effect that demonstrated positive transfer to electrical kindling. A brief outline of results obtained in transfer studies since 1969 is presented. The general conclusion is that the great majority of tests of transfer have resulted in evidence of positive transfer. The clinical relevance of kindling and transfer is outlined. A hypothetical model of transfer mechanisms is outlined. The suggestion is that the transfer effect depends most basically on neuroplastic changes in midbrain or brainstem reticular areas into which forebrain epileptiform activity feeds.
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PMID:Transfer of kindling: clinical relevance and a hypothesis of its mechanism. 408 81

Infantile spasms constitute a severe seizure disorder unresponsive to standard anticonvulsants. Both prednisone and adrenocorticotropic hormone (ACTH) have produced remission of seizures in some patients. The mechanisms of action of these hormones are not known. Eight infants with infantile spasms were treated with prednisone for 2 weeks. This controlled the seizures in two patients. In the remaining six patients, prednisone was continued and ACTH was added. This treatment produced cessation of spasms in four patients. Serum prednisone and cortisol were measured at a number of points during treatment. In infants receiving prednisone and then prednisone plus ACTH, serum cortisol was suppressed to about one-quarter of baseline levels with the initiation of prednisone, and remained suppressed during ACTH administration. We conclude that ACTH can exert its effect on infantile spasms in the setting of adrenal suppression, and can act without stimulating endogenous cortisol production. A CNS site of action is suggested and should be sought.
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PMID:Adrenocorticotropic hormone controls infantile spasms independently of cortisol stimulation. 609 Jan 11

Both opioid peptides such as beta-endorphin and met-enkephalin and nonopioid peptides such as vasopressin and oxytocin increase pain thresholds in rodents. Antisera raised against each of these peptides have been developed for use in immunocytochemical and radioimmunoassay procedures. The present study assessed whether central administration of antisera raised against beta-endorphin (ABE), met-enkephalin (AME), arginine, vasopressin (AAVP) or oxytocin (AOT) altered tail-flick latencies elicited by three different levels of radiant heat, jump thresholds, core body temperatures and locomotor activity. ABE induced a transient hyperalgesia on the tail-flick test at thermal levels at which beta-endorphin administration would elicit an analgesic effect. While met-enkephalin increases tail-flick latencies elicited by high thermal levels, AME failed to alter latencies at this level, but rather induced a short-acting hyperalgesia at a low thermal level. While vasopressin increased tail-flick latencies at high thermal levels, AAVP produced reciprocal decreases. Yet AAVP inexplicably induced analgesic effects at moderate and low thermal levels. Finally, while oxytocin increased latencies at high thermal levels, AOT failed to alter latencies. Rather, it decreased latencies at the moderate thermal level and increased latencies at the low thermal level. Neither jump thresholds nor core body temperatures were affected by any antiserum pretreatment. While activity levels were unaffected by either ABE, AME or AAVP pretreatment, AOT decreased activity in a fashion complementry to oxytocin-induced hyperactivity and seizures. There data are discussed in terms of tonic versus phasic influences of these peptides upon pain perception.
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PMID:Pain threshold changes in rats following central injection of beta-endorphin, met-enkephalin, vasopressin or oxytocin antisera. 609 76

As more small peptidergic components of the central nervous system are isolated, their role in disease states is being investigated. Several of these neuropeptides, especially the opioidlike peptides, adrenocorticotropic hormone, and some hypothalamic releasing factors, have been found to alter neuronal excitability. This finding has led to the proposal that these peptides may play a role in the pathogenesis of the epilepsies. We tested this hypothesis in a genetic model of epilepsy. At nontoxic doses, several exogenously administered peptides had anticonvulsant properties, while others were proconvulsant. The most potent anticonvulsant was the opioidlike peptide beta-endorphin. Its effect was similar to that of the opioid alkaloids. Using the potent antagonist naloxone hydrochloride to block possible endogenous opioid-like peptides, we found no effects on seizures in naive animals. Naloxone did alter postictal events, however, by partially blocking the postictal refractoriness to further seizures. We speculate that one possible role for the endogenous opioid peptides may be to limit the spread of seizures or to modulate postictal susceptibility to further seizures. Naloxone was effective in this model only after stressful situations occurred that modified the seizures and presumably induced a release of endogenous opioidlike peptides. Support for this hypothesis from other epilepsy models is discussed. Other peptidergic systems may also be active in various epileptic models, and the current understanding of their roles is reviewed.
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PMID:Neuropeptides: a role as endogenous mediators or modulators of epileptic phenomena. 609 40

ACTH and cortisol were measured simultaneously in plasma samples obtained every 5 min from subjects at two different diurnal times. In the first study adrenocorticotropic hormone (ACTH) mean concentration and secretory rate were elevated in anticonvulsant drug-treated temporal lobe epileptic patients in comparison to anticonvulsant drug-treated patients with pseudoseizures. Cortisol mean concentrations and secretory rate were similar in these groups of subjects. In the second study, mean ACTH concentration and secretory rate were higher in temporal lobe epileptic patients than in normal controls. Both measures of ACTH secretion were similar in post-temporal lobectomy patients and normal controls. Mean cortisol concentration and secretory rates were highest in the temporal lobe epileptic patients, lowest in normal controls, and intermediate in post-temporal lobectomy patients. We conclude that ACTH and cortisol secretion is abnormal in temporal lobe epileptic patients. Temporal lobectomy restores abnormal ACTH secretion to normal whether or not seizures are controlled. The absence of ACTH changes in the pseudoseizure patients suggests that these changes are not drug induced. Cortisol secretion is similar in temporal lobe epileptic patients and pseudoseizure patients, suggesting a direct effect of the drugs upon the adrenal cortex.
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PMID:Pituitary and adrenal function in epileptic patients. 609 18

The influence of amygdaloid kindling on brain and pituitary content of immunoreactive dynorphin (IR-DYN) and other opioid peptides was studied in rabbits. The kindling was very effective in increasing the hippocampal levels of IR-DYN, alpha-neoendorphin and Leu-enkephalin, but remained without any significant effect on the levels of IR-DYN and beta-endorphin in the majority of brain structures studied. The concentration of IR-DYN in the hippocampus remained at the control level throughout the development but was increased dramatically after completion of kindling. Biochemical alterations persisted for at least one month following the completion of kindling. The obtained results suggest that the hippocampal IR-DYN and related peptides may play some role in the maintenance of amygdaloid-kindled seizures.
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PMID:Opioid peptides, particularly dynorphin, after amygdaloid-kindled seizures. 613 21

The naturally epileptic Mongolian gerbil was used to investigate the epileptogenic properties of beta-endorphin, dynorphin, met-enkephalin and morphine. The results indicate that opioid induced "seizures" are different from naturally spontaneous seizures in the gerbil in respect to EEG recording and motor behavior. Evidence for a protective role in preventing seizures is also presented.
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PMID:Opioid peptides and seizures in the spontaneously epileptic Mongolian gerbil. 614 1


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