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)

In idiopathic or generalized epilepsy, serum glucose and cholesterol concentrations tend to be low, especially just before the seizure. Glucose tolerance curves are abnormal and variable. The electrolyte balance is disturbed, and epileptics tend to go readily into alkalosis. Serum [Na+] is usually unaffected, but [K+] is normal to low between attacks and increases during and after the seizure. Serum [Cl-] is usually high just before the seizure. Epileptics are generally mildly hypocalcemic, especially in the period before the seizure. Serum urea and nonprotein nitrogen values are low between paroxysms but increase after the seizure. Serum protein concentration is usually normal. Stress, which releases epinephrine and corticotropin, results in high serum citrate concentration, which probably contributes to decreased serum [Ca2+] just before a seizure. In the healthy individual, any increase in serum citrate is accompanied by increasing [Ca2+]. In the rabbit, convulsions can be induced with corticotropin, a result of increased serum citrate concentration coupled with a decrease in [Ca2+]. The net result is severe hypo-ionic-calcemia. A similar phenomenon has been reported in a few humans. Administration of insulin causes serum citrate concentrations to decrease. Apparently, the dynamic system that controls glucose and lipid metabolism, and thus electrolyte balance, through the hormones epinephrine, corticotropin, insulin, glucagon, calcitonin, and parathormone, is abnormal in the epileptic.
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PMID:Clinical biochemistry of epilepsy. I. Nature of the disease and a review of the chemical findings in epilepsy. 22 Nov 36

We propose than an alarm mechanism is operative in animals, designed to regulate neuromuscular irritability by regulating [Ca2+]. Epinephrine or corticotropin (ACTH), injected intramuscularly into animals, causes a hypercitricemia, resulting in decreased [Ca2+]. This increases muscular excitability to facilitate escape. To avoid over reaction, [Cl-] is shifted into the plasma without a concomitant shift of Na+, thus generating an acidosis and an increase in ionization of Ca. Plasma pH, pCO2, total CO2, and [K+] decrease, and [Mg2+] increases. The acidosis, decrease in K+, and increase in [Mg2+] serve to counteract the effect of the decrease in [Ca2+], to protect against tetany. In the rabbit the hypercitricemia observed upon ACTH administration is accompained by a severe hypocalcemia and drop in blood pressure, resluting in tetanic convulsions. This seems to indicate calcitonin release, independent of the hypercitricemia. Thyroidectomized rabbits show only mild hypocalcemia when given ACTH, but develop a severe acidosis and typical grand mal epileptiform seizures. Administration of ACTH and then calcitonin to the goat, an animal resistant to the effects of ACTH alone, simulates the effect observed in the rabbit with respect to changes in blood components and blood pressure. Changes in the blood in the goat and rabbit resemble those in humans before an epileptic seizure. alpha-Melanotropin, containing a portion of the ACTH sequence, reacts in a manner similar to ACTH but more rapidly.
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PMID:Clinical biochemistry of epilepsy. II. Observations on two types of epileptiform convulsions induced in rabbits with corticotropin. 22 Nov 37

There is a growing body of evidence suggesting that corticosteroids contribute to the increased neural excitability observed during ethanol withdrawal. In the present study, this was further investigated using mouse strains which differ in ethanol withdrawal severity. DBA/2 (DBA) mice were found to display more severe acute ethanol withdrawal seizures than C57BL/6 (C57) mice. Additionally, DBA mice showed a greater stress response than C57 mice, as measured by higher plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, to an acute dose of ethanol. Mimicking withdrawal plasma corticosterone levels by administering corticosterone to ethanol-naive mice resulted in increases in handling-induced convulsions in the range observed during withdrawal. There did not appear to be a strain difference in sensitivity to the excitatory effects of corticosterone. In summary, the greater stress response to ethanol by DBA mice may account, in part, for the more severe ethanol withdrawal syndrome of this strain.
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PMID:Genetic differences in hypothalamic-pituitary-adrenal axis responsiveness to acute ethanol and acute ethanol withdrawal. 132 Sep 85

It was shown in the experiments on rats that the repeated picrotoxin administration resulted in the kindling of generalized seizures. Generalized convulsions were followed by the development of either postictal depression or explosiveness. The injection of mu-opiate agonist met-enkephalin into hippocampus of kindled rats resulted in the increase in the severity of seizure reactions which were induced by picrotoxin and also in the increase in the number of animals with postictal explosiveness. The injection of dynorphin-A-1-13 (kappa-opiate agonist) into substantia nigra reticulata induced the locomotor depression which was like one in postictal period and resulted in the decrease of picrotoxin-induced seizures severity. It was concluded that mu-opiate system of hippocampus took part in the formation of generator of pathologically enhanced excitation in the structure during kindling and the development of seizure syndrome, providing also the postictal explosiveness. Kappa-opiate system of substantia nigra plays an important role in the activation of the antiepileptic system, limitation of seizures and the development of postictal depression.
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PMID:[The role of the opiate mechanisms of the hippocampus and substantia nigra in the behavioral and convulsive disorders in picrotoxin-induced kindling]. 167 96

D-Tyr-Ser-Gly-Phe-Leu-Thr (DSLET), beta-endorphin, morphiceptin and morphine were microinjected at 48-h intervals into the amygdala or hippocampus of awake rats in an attempt to identify the opiate receptor types involved in opioid kindling. DSLET, beta-endorphin, morphiceptin and morphine were injected into the lateral ventricle to assess the possibility of kindling seizures by this route. The delta-receptor agonist DSLET effectively kindled convulsions when microinjected into amygdala or ventral hippocampus. The convulsions were suppressed or strongly attenuated by ICI 174,864, a specific antagonist of the delta-receptor, microinjected into the same brain site, but were not affected by ICI 174,864 administered peripherally. When microinjected into amygdala or hippocampus, beta-endorphin and morphiceptin also kindled convulsions, which were antagonized by naloxone but not by ICI 174,864. Morphine evoked EEG epileptiform activity but did not kindle convulsions from limbic brain sites. DSLET occasionally evoked epileptiform spiking and submaximal convulsions when injected into ventricle, and morphiceptin evoked epileptiform spiking only, but tolerance to these effects occurred after repetition of the injections. Thus, convulsions can be kindled by activation of either mu-, delta- or epsilon-receptors when opioids are injected directly into limbic tissue. However, the ability of these compounds to kindle seizures is markedly reduced when they are administered into ventricle. The striking differences between the present results and previous results obtained by peripheral or intraventricular administration of opioid peptides suggest that the route of administration, among other variables, is a crucial factor in assessing the epileptogenic properties of opioid peptides.
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PMID:Involvement of multiple opiate receptors in opioid kindling. 216 33

To evaluate the nature of anterior pituitary secretory events in vivo, we have applied a novel waveform-independent deconvolution technique that dissects the underlying secretory behavior of endocrine glands quantitatively from available serial plasma hormone concentration measurements assuming one- or two-compartment elimination kinetics. We used this new tool to ask the following physiological questions. 1) Does the pituitary gland secrete exclusively in randomly dispersed bursts, and/or does a tonic (constitutive) mode of interburst hormone secretion exist? 2) What secretory mechanisms generate the nyctohemeral rhythms in plasma hormone concentrations? Analysis of 24-h plasma concentration profiles of GH, LH, FSH, PRL, TSH, ACTH, and beta-endorphin (n = 6-8 men/group) revealed that 1) pituitary secretion in vivo occurs in an exclusively burst-like mode for all hormones except TSH and PRL (for the latter two, a mixed burst and constitutive mode pertained); 2) significant nyctohemeral regulation of secretory burst frequency alone was not demonstrated for any hormone; 3) prominent 24-h variations in secretory burst amplitude alone were delineated for ACTH and LH; 4) TSH, GH, and beta-endorphin were both frequency and amplitude controlled; 5) no significant diurnal variations in FSH secretory parameters occurred; and 6) a fixed hormone half-life yielded fits of the 24-h data series with a normalized residual variance of less than 8%. We conclude that the normal human anterior pituitary gland releases its multiple (glyco)protein hormones via punctuated secretory episodes unassociated with tonic basal (constitutive) hormone secretion, except in the case of TSH and PRL. Hormone-specific amplitude and/or frequency control of secretory burst activity over 24 h provides the mechanistic basis for the classically recognized 24-h rhythms in plasma concentrations of adenohypophyseal hormones in men.
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PMID:Twenty-four-hour rhythms in plasma concentrations of adenohypophyseal hormones are generated by distinct amplitude and/or frequency modulation of underlying pituitary secretory bursts. 217 82

To determine whether the effect of electroacupuncture (EA) on electroconvulsive shock (ECS) was through affecting endogenous opioid peptidergic system in the hippocampus, we used radioimmunoassay (RIA) to measure leu-enkephalin- and beta-endorphin-like immunoreactivity (L-E-LI and Beta-E-LI) in the hippocampal perfusate after ECS and EA treatments. Wistar rats were given ECS stimulation, which caused behavioral and electroencephalogram (EEG) convulsions. However, EA could suppress ECS-elicited convulsions (including both behavioral and EEG abnormalities). The results of RIA showed that after repeated ECS treatments, the contents of L-E-LI and Beta-E-LI increased significantly by 136% and 157%, respectively. In contrast, EA treatment depleted alterations of L-E-LI and Beta-E-LI induced by ECS, depleting L-E-LI by 32% and Beta-E-LI by 85%. These observations suggest that anticonvulsive action of EA is related to the release of L-E and Beta-E in hippocampus, probably through decreasing their release, thus to exert EA action.
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PMID:Change of Leu-enkephalin- and B-endorphin-like immunoreactivity in the hippocampus after electroconvulsive shock and electroacupuncture. 257 44

Corticotropin-releasing factor (CRF) and its related peptides have some conserved primary regions. We have taken an interest in the characteristic conserved sequence, Pro-Pro-Ile-Ser, which is located in the proximal N-terminal region of the CRF family. This sequence is not included in any other biologically active peptide and protein. Biological function of this N-terminal region has not become known yet. We synthesized seventeen peptide fragments of human CRF and sauvagine which involved either this entire N-terminal sequence or part of it and determined their behavioural effect after intracerebroventricular injections to mice. Several peptides which included the Pro-Pro-Ile region as the N-terminal segment and their caused a transient convulsion dose-dependently. H-Pro-Pro-Ile-OH (human CRF(4-6)) exhibited the strongest effect among these active peptides. However, these convulsant peptides did not affect the secretion of immunoreactive corticotropin in rats.
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PMID:Convulsant peptides related to corticotropin-releasing factor (CRF). 259 51

The permeability of the blood-brain barrier (BBB) to immunoreactive alpha-melanotropin (alpha-MSH) was quantified in rats pretreated with monosodium L-glutamic acid to deplete their CNS stores of endogenous alpha-MSH. The methodology, suitable for poorly permeable substances, monitored blood and brain tissue concentrations of alpha-MSH over 15 min following intravenous injection of 30 nmol synthetic alpha-MSH. Rate constants for entry of alpha-MSH into brain tissue were estimated from separate non-linear least-squares fits of connecting two- and one-compartment open models to plasma and extravascular brain tissue concentration data, respectively. Comparisons were made to rate constants measured similarly for 14C-inulin. The BBB had a low permeability to immunoreactive alpha-MSH, consistent with peptide penetrating the barrier by passive diffusion dependent upon the lipid solubility of the molecule.
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PMID:Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive alpha-melanotropin. 285 21

Neuropeptides represent a new class of compounds with important implications for the understanding of the mechanisms and treatment of epileptic disorders. Several systems of peptide modulators--in particular the opioid-like peptides, vasopressin, somatostatin, thyrotropin-releasing hormone (TRH) and ACTH--have partially demonstrated endogenous roles in some forms of epilepsy. Seizures and stressful situations may release endogenous opioid peptides and mediate postictal depression and postictal seizure refractoriness. Vasopressin is believed to increase susceptibility to convulsions and may be involved in the pathogenesis of febrile convulsions. Derangements in TRH regulation may lower thresholds for seizure expression by regulating arousal systems; however, some TRH analogs have proven to be effective anticonvulsants. Long-term alterations in somatostatin regulation could be components of focal epilepsies. ACTH is particularly useful in the treatment of infantile spasms. Pharmacological effects of these and other peptides have potentials for defining new classes of anticonvulsants. Cholecystokinin (CCK) and its analogs, the opioid peptides beta-endorphin and FK33824, TRH analogs, and several dipeptides exhibit potent anticonvulsant properties in chemical, electroshock, and genetic model screens. Convulsant actions of CRF, somatostatin, TRH, vasopressin, and high doses of endorphin or enkephalins may provide new tools to study regulatory mechanisms of cerebral excitability. The enkephalin epileptogenic effect is being developed as a predictive tool for new anti-petit mal anticonvulsants. Advances in molecular biology have identified the genes of particular peptide families. A concept has developed that the large propeptide precursors, coded by these genes, whose processing leads to functional peptide formation and release, regulate peptidergic humoral responses to external stimuli. This idea may have particular application in the understanding of the genetic basis of some seizure states. Techniques for amplification of mRNA expression have identified specific neuronal proteins and peptides. Knowledge of protein and propeptide structural cleavage sites has suggested previously unknown candidates for modular systems in epileptic states. Technological advances in automated peptide sequencing and synthesis have allowed the development of metabolically resistant analogs and antagonist peptides. The anticonvulsant potencies of CCK, TRH, and opioid peptides have been defined more clearly with these methods.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. 287 23


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