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)

The central enzymatic stability of des-enkephalin-gamma-endorphin and its synthetic analogs [cycloN alpha 6, C delta 11]beta-endorphin-[6-17] and [Pro7, Lys(Ac)9]-beta-endorphin[6-17] was studied in vitro using a newly developed, regionally dissected rat brain slice, time course incubation procedure. Tissue slice viability was estimated as the ability of the brain slice to take up or release gamma-[3H]aminobutyric acid after high K+ stimulation. Results demonstrated stability of uptake/release up to 5 hr of incubation, suggesting tissue viability over this period. The estimated half-life of peptides based on the results obtained in our incubation protocol suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. A good correlation exists between the high enzyme activity of neutral endopeptidase (EC 3.4.24.11) and the rapid degradation of des-enkephalin-gamma-endorphin and [cycloN alpha 6, C delata 11]beta-endorphin-[6-17] in caudate putamen. Proline substitution combined with lysine acetylation appears to improve resistance to enzymatic metabolism in caudate putamen and hypothalamus. However, cyclization of des-enkephalin-gamma-endorphin forming an amide bond between the alpha-NH2 of the N-terminal threonine and the gamma-COOH of glutamic acid did not improve peptide stability in any brain region tested. The present study has shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of rat brain where peptides, peptidases and receptors are colocalized and that specific structural modifications can improve peptide stability.
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PMID:Neuropeptide processing in regional brain slices: effect of conformation and sequence. 214 Jan 32

1. Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several peptides at the carboxyl side of proline residues. Because brain contains relatively large amounts of this enzyme and because of its specificity it has been suggested that it plays a role in the metabolism of neuropeptides, acting both on their processing and their degradation. 2. Since the final steps of neuropeptide processing occur in the synaptic vesicles and the degradation of most of these peptides is believed to occur in the synaptic cleft, we studied the distribution of proline endopeptidase activity in sub-fractions of rat hypothalamus. 3. Proline endopeptidase activity is present in synaptosomal fractions and is released by hypo-osmotic shock. Its specific activity is higher in the synaptoplasma than in synaptic membranes or vesicles (7.98 vs 0.18 and 0.24 nmol min-1 mg protein-1 carbobenzoxy-glycyl-prolyl-sulfamethoxazole hydrolysis). 4. Inhibitory avoidance training, a situation which releases hypothalamic vasopressin and beta-endorphin, both in vitro substrates, did not affect the specific or total activity of proline endopeptidase in synaptosomal plasma membranes.
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PMID:Distribution of proline endopeptidase activity in sub-synaptosomal fractions of rat hypothalamus. 330 57

Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several neuropeptides at the carboxyl-side of proline residues. Some peptide substrates of this enzyme may be found in the rat hypothalamus (thyrotropin releasing hormone, neurotensin, substance P, oxytocin, vasopressin, beta-endorphin). Recent research has shown that the hypothalamic levels of some of these substances (e.g., vasopressin, beta-endorphin) change by a variety of training procedures. We studied the effect of various forms of training on the activity of proline endopeptidase of rat hypothalamus. The present results show that the activity of this enzyme is not altered by electroconvulsive shock or inhibitory avoidance training when measured, 0, 1, or 3 hr after these procedures. Other behavioral procedures (habituation to an open field, two-way active avoidance conditioning, or 1 min of inescapable footshock) also had no effect on hypothalamic proline endopeptidase activity measured immediately after training or test sessions. We conclude that proline endopeptidase probably does not play a regulatory role in the effect of synaptically released hypothalamic neuropeptides on behavior.
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PMID:Hypothalamic proline endopeptidase activity is not changed by various behavioral procedures. 353 16