B-ETA-Endorphin immunoreactivity in rat and human blood: radioimmunoassay, comparative levels and physiological alterations.
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Biomedical subjects
Publications and source records attributed to J D Barchas.
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With the discovery of the opiate peptides, several major avenues of research became apparent. These peptides produced a great deal of focused attention on their anatomy, biochemistry, and physiology. In this article, we present an overview of some of the main research issues and recent findings in the field of opiate peptides. The possible relationship of the opiate peptide neuronal systems to schizophrenia is discussed in light of attempts to alter schizophrenic symptoms with opiate antagonists, beta-endorphin, and dialysis. It is hypothesized that if the opiate peptides are involved in schizophrenia, then their involvement with dopamine systems and/or with stress responses may be critical.
Beta-endorphin, morphine, and saline were given intravenously to a single schizophrenic subject on separate occasions in a double-blind design. EEG spectral analyses performed on data collected before and after drug injection demonstrated that beta-endorphin and morphine produced similar increases in alpha power within 5 to 15 minutes after injection. This effect could be distinguished from two placebo (saline) injections. These data suggest that intravenous beta-endorphin can produce changes in the central nervous system in humans.
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Enkephalin-like activity has been measured in the ventricular cerebrospinal fluid of patients with intractable pain. Electrical stimulation of periventricular brain sites resulted in significant decrease in persistent pain in these subjects. This analgesia, which was blocked by naloxone in 80% of the cases, was accompanied by a significant rise in ventricular enkephalin-like activity, as measured by two different methods. The results present evidence of in vivo release of enkephalin-like material in humans and suggest that stimulation analgesia may be partially due to this release.
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Endogenous opiate-like peptides (endorphins) are putative neuroregulators located throughout the mammalian brainstem. There is some evidence for their role in pain, stress, and affect. We report that the opiate antagonist, naloxone, alters some schizophrenic symptoms. In a double-blind, cross-over study, naloxone produced decreases in auditory hallucinations in some schizophrenic patients. This finding supports the hypothesis that the endorphins may play a roll in modulating hallucinations in a highly selected subgroup of chronically hallucinating schizophrenic patients.
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By means of antiserum (purified by affinity chromatography) directed against adrenocorticotropin (ACTH) 11-24, cell bodies and beaded axons were visualized in rat brain. The ACTH-like immunoreactivity (ACTH-LI) was primarily located in the hypothalamus (cells and axons). Fibers were scattered throughout thalamus, amygdala, periaqueductal gray area, and reticular formation. There was no change in the distribution of ACTH-LI in rats that had been subjected to hypophysectomy. This distribution of ACTH-LI parallels that of beta-lipotropin and is altered by specific lesions in a similar fashion. The presence of ACTH-LI in cells and beaded axons in brain raises the possibility that it is a neuroregulator functioning as a neurotransmitter, neuromodulator, or neurohormone.
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There is compelling evidence that behavioral events after neurochemical function and that altered neurochemical function can change behavior. Such processes have been related both to neurotransmitters and to neuromodulators, together termed neuroregulators. Available research tools and theoretical constructs have begun to permit studies of certain types of behavior, primarily those related to emotional states and drives. This work is changing long-held concepts about severe mental disorders and the treatment of them.
A selective ion monitoring assay for probenecid (p-(dipropylsulfamyl)benzoic acid) using m-(di-isobutylsulfamyl)benzoic acid as an internal standard is described. The method has been applied to the determination of probenecid concentrations in human cerebrospinal fluid and lends itself to incorporation into the selective ion monitoring procedures used to quantitate other acidic and neutral compounds in such samples.
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The effects of 5-hydroxytryptophan (5-HTP), a serotonin precursor, and carbidopa, a peripheral aromatic amino acid decarboxylase inhibitor, were studied in a boy with the Lesch-Nyhan syndrome. No effects on the self-mutilating behaviors of this disorder were noted. However, sleep patterns were normalized, with a reduction in the proportionate amounts of wakefulness and an augmentation of active sleep. A sharp reduction in waking behavioral dyskinesias was also correlated to increased drug dosage.
beta-Endorphin-like immunoreactivity in human ventricular cerebrospinal fluid was measured with a specific radioimmunoassay. The subjects were undergoing a surgical procedure for relief of chronic intractable pain. This procedure involved the focal stimulation of a medial thalamic site adjacent to the wall of the third ventricle. Samples were collected before and during the analgesic stimulation. No beta-endorphin-like immunoreactivity could be detected prior to stimulation, suggesting that baseline levels are below 25 fmol/ml of cerebrospinal fluid. Electrical stimulation led to substantial increases (13- to 20-fold) in immunoreactive material in every subject. These results suggest that beta-endorphin-like material can be released into the ventricular system and may contribute to the pain blockade that results from periventricular stimulation.