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)

Developmental and long-term behavioral effects of perinatal injection of beta-endorphin (BE), CRF and Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1) in male rats were investigated along with the possibility that opiate receptors may be altered by the injection of BE during this critical time. Daily injections of peptide were given to pregnant females (100 micrograms/rat) in the week before birth or to the offspring (50 micrograms/rat) of untreated mothers during the first week of life. Prenatal BE and CRF reduced body weight on day 1, in contrast to Tyr-MIF-1 which produced a significant increase over controls by day 7 as well as a slight but significant acceleration of eye opening. Among the postnatal treatments, CRF-treated animals showed the most dramatic changes. These included decreased body weight, accelerated eye opening, and, in adulthood, increased open field rearing behavior and a tendency for a monotonic body temperature response to low doses of morphine, in contrast to the biphasic response shown by controls. BE, when given to pregnant mothers, increased the number (Bmax) of [3H]naloxone-labeled (mu) receptors in whole brains of offspring assayed on day 14, but it did not significantly alter [3H]D-Ala-D-Leu-enkephalin-labeled (delta) receptors. In contrast, a significant decrease in both mu and delta receptors was observed on day 14 in rats given BE postnatally. These differences in receptors were no longer apparent in adulthood, and no significant differences in tail-flick response were detectable at this time. Nevertheless, some of the effects of these three peptides endured well beyond their presence, and for BE included changes in the number of opiate receptors.
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PMID:Developmental, behavioral, and opiate receptor changes after prenatal or postnatal beta-endorphin, CRF, or Tyr-MIF-1. 286 78

In order to clarify the effects of endogenous opiate peptides on the vasopressin system, we have investigated the presence of different opiate receptor subtypes in the neurohypophysis by radioreceptor assay and autoradiography. [3H]-etorphine binding to membrane preparations revealed the presence of high- and low-affinity binding sites (KD, 1.2 nM and 8.1 nM). Displacement of [3H]-etorphine by opiate receptor subtype-specific ligands gave the following results: the preferential mu agonists DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-oL) and the tetrapeptide morphiceptin did not displace etorphine; the preferential sigma receptor agonists DADLE (D-Ala2,D-Leu5-enkephalin) or DSTLE (D-Ser2,Leu5,Thr6-enkephalin) and beta-endorphin, a preferential agonist of the epsilon receptor, displaced [3H]-etorphine from its low-affinity site only, and dynorphin 1-8, a preferential kappa agonist, displaced [3H]-etorphine from its high-affinity binding site. Film autoradiography of neurohypophyseal sections incubated with [3H]-etorphine showed a displacement of 30% of the labeled ligand by unlabeled dynorphin 1-8. Exposure of rat neurointermediate lobes in organ culture to dynorphin 1-8 caused a small but significant stimulation of vasopressin release. These results demonstrate the existence of dynorphin 1-8 sensitive opiate receptors of the kappa subtype in the neurohypophysis and their possible involvement in vasopressin release.
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PMID:Dynorphin 1-8 binds to opiate kappa receptors in the neurohypophysis. 287 1

Beta-endorphin immunoreactivity was measured in plasma and hypothalamus of rats treated with alpha-methyl-p-tyrosine (alpha -MT) (two doses of 200 mg/kg) or p-chloro-phenyl-alanine (PCPA) (two doses of 150 mg/kg). It was also measured in plasma after a single dose (5 mg/kg) of amphetamine or after electrical stimulation of median raphe nucleus (MRN). Plasma levels of immunoreactive beta-endorphin (ir B-E) were significantly decreased by PCPA and were elevated by electrical stimulation of MRN. Alpha -MT was ineffective to modify ir B-E plasma concentration as well as amphetamine. These findings suggest a role for 5-hydroxytryptamine (5-HT) in the regulation of plasma B-E content.
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PMID:Involvement of a serotonergic control in the regulation of plasma levels of immunoreactive beta-endorphin. 287 72

Since both aminopeptidases and angiotensin I-converting enzyme are reported to degrade circulating enkephalins, we have examined the degradation of low-molecular-weight opioid peptides by a vascular plasma membrane-enriched fraction previously shown to contain both angiotensin I-converting enzyme (EC 3.4.15.1) and aminopeptidase M (EC 3.4.11.2). Except for an enkephalin analog resistant to amino-terminal hydrolysis, [D-Ala2]enkephalin, the purified vascular plasma membrane preferentially degraded low-molecular-weight opioids by hydrolysis of the N-terminal Tyr-1--Gly-2 bond. Enkephalin degradation was optimal at pH 7.0 and was inhibited by the aminopeptidase inhibitors amastatin (I50 = 0.08 microM), bestatin (9.0 microM) and puromycin (80 microM). Maximal rates of hydrolysis, calculated per mg plasma membrane protein, were highest for the shorter peptides (18.3, 15.6 and 16.6 nmol/min per mg for Met5-enkephalin, Leu5-enkephalin and Leu5-enkephalin-Arg6, respectively) and decreased with increasing peptide length (0.7 nmol/min per mg for dynorphin (1-13)). No significant hydrolysis of beta- and gamma-endorphin was detected. Km values decreased significantly with increasing peptide length (Km = 72.9 +/- 2.7, 43.6 +/- 4.7 and 21.4 +/- 0.9 microM for Met5-enkephalin, Leu5-enkephalin-Arg6 and Met5-enkephalin-Arg6-Phe7, respectively). However, no further decreases were seen with even larger sequences, i.e., dynorphin(1-13). Other peptides hydrolyzed by the plasma membrane aminopeptidase (angiotensin III, kallidin and hepta(5-11)-substance P) inhibited enkephalin degradation in a competitive manner. Thus, localization, specificity and kinetic data are consistent with identification of aminopeptidase M as a vascular enzyme with the capacity to differentially metabolize low-molecular-weight opioid peptides within the microenvironment of vascular cell surface receptors. Such differential metabolism may play a role in modulating the vascular effects of peripheral opioids.
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PMID:Degradation of low-molecular-weight opioid peptides by vascular plasma membrane aminopeptidase M. 287 42

The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe (-Met/-Leu at their amino-terminus. Three distinct families of these peptides (beta-endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). Met-enkephalin, Leu-enkephalin and the related heptapeptide Met-enkephalin-Arg6-Phe7 and octapeptide Met-enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structures of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. At the present time the main question concerns the physiological significance of such a great diversity of endogenous opioid peptides.
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PMID:[Discovery, anatomical mapping and biosynthesis of various families of endogenous opioid peptides]. 287 7

Clinical prospects of an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin (DT gamma E) in schizophrenia were examined by using the Brief Psychiatric Rating Scale (BPRS) and the electroencephalogram (EEG). Twelve inpatients with chronic schizophrenia were administered fixed doses of neuroleptics throughout the study. Six patients were treated with DN-1417 (DN-1417 group), and the remaining 6 patients with DT gamma E (DY gamma E group). One mg/day of DN-1417 or DT gamma E was given intramuscularly for 2 consecutive weeks followed by 1 week of no drug treatment. In the DN-1417 group, both total BPRS scores and scores on hallucinatory behaviour and unusual thought content decreased in the first and third weeks. The power values of alpha and beta activities from the frontal area increased in the first and third weeks, whereas an increase in alpha activity and a decrease of high-fast beta activity from the occipital area were obtained during the study. On the other hand, the DT gamma E group failed to show either a decrease in BPRS scores or any remarkable EEG changes except for a slight decrease in beta activity. These results suggest that the positive symptoms of schizophrenia are improved by DN-1417 treatment, and that the alterations in BPRS scores coincide with changes in the frontal EEG.
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PMID:A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin in schizophrenia. 288 64

Male rats were injected s.c. once daily during the first week of life with beta-endorphin (BE), morphiceptin, the antiopiate Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), or one of the two opiate peptides in combination Tyr-MIF-1. Pups treated with neonatal BE removed their tails from a series of increasingly hot water baths significantly faster than controls on day 9, confirming our earlier studies. In addition, we found that Tyr-MIF-1 blocked this effect of BE. At 4.5 months, latency to lick a hindpaw in the hot-plate test was significantly faster in groups given BE alone, morphiceptin alone, or the control vehicle than in any of the 3 groups given Tyr-MIF-1. At 6 months the two groups given opiate peptides alone showed faster tail-flick latencies than the controls and the groups given Tyr-MIF-1. These results indicated that the long-term nociceptive changes induced by the opiate peptides were opposite to those induced by Tyr-MIF-1. Mean tail-flick latencies of the groups on day 9 correlated well with hot-plate and tail-flick scores in adulthood, indicating that the effects of the peptides were persistent. The neonatal peptide treatments did not differentially affect the analgesia induced by the stress of footshock or warm-water swim. Rats given either of the opiate peptides alone tended to fall off a rotorod faster than those in the other groups. These results support the role of Tyr-MIF-1 as an antiopiate and further illustrate the long-term effects of neonatally administered peptides.
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PMID:Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1. 288 15

The blood-brain barrier is capable of transporting peptides with anti-opiate (Tyr-MIF-1) and opiate (enkephalins) activity out of the central nervous system. The relationship of this transport system to the various actions of opiates remains unexplored. This study examined the relationship between the rate of transport and opiate-induced analgesia. Both restraint, a stress that provokes an opiate-mediated analgesia, and the administration of morphine (12 mg/kg, i.p.) each induced an inhibition in the rate of transport. Such inhibition exhibited specificity, since the saturable, brain to blood transport of iodide remained unaltered. However, it was possible to dissociate analgesia and inhibition of transport. The onset and peak of analgesia, as measured by tail-flick latency induced by morphine, preceded the onset and peak of the inhibition of transport. Naltrexone, which blocks opiate-mediated analgesia, also induced inhibition of transport without any significant effect on tail-flick latency. (-) Naloxone but not (+) naloxone also weakly inhibited transport. Deprivation of food and water, associated with analgesia possibly mediated by the opiate, beta-endorphin, which is not transported out of the brain by this system, did not alter transport. These results suggest that while inhibition of transport and analgesia may occur together, these events probably represent two separate aspects of the action of opiates, that may even be mediated by separate receptor sites or peptides in the opiate family.
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PMID:Analgesia and the blood-brain barrier transport system for Tyr-MIF-1/enkephalins: evidence for a dissociation. 289 31

The degradation of opioid peptides by human placental aminopeptidase M was studied by measuring liberated amino acids by high performance liquid chromatography. The purified placental aminopeptidase M actively degraded Met-enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk) completely into constituent 5 amino acids. The activities as a function of tyrosine liberation were observed for Met-Enk followed by Leu-Enk, beta-neoendorphin, dynorphin, and beta-endorphin.
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PMID:In vitro degradation of opioid peptides by human placental aminopeptidase M. 290 92

The presence of tertiary structure in aqueous solutions of the amino-terminal nine- and seventeen-residue analogues of human beta-endorphin has been further demonstrated by leucine aminopeptidase (LAP) cleavage of the amino-terminal tyrosine. The reactions were followed by difference absorption spectroscopy. While the amino-terminal pentapeptide showed no resistance to LAP action, the nonapeptide displayed definite resistance. The heptadecapeptide analogue was found to be completely refractory to LAP action under the conditions employed. Thermolysin cleavage of the Phe4-Met5 bond in the longer analogues destroys the tertiary structure, not only removing the previously reported red shift in tyrosine absorption but also resulting in complete normalization to LAP digestion.
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PMID:Tertiary structure in deletion analogues of human beta-endorphin: resistance to leucine aminopeptidase action. 293 85


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