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At least 37 records · Page 2Linked to original sources
PubMed1984

Beta-endorphin-related peptides in the human pituitary. Isolation and characterization of major immunoreactive peptides, including the formerly unrecognized peptide beta-endorphin 1-18.

The qualitative and quantitative aspects of beta-endorphin-related peptides present in the human pituitary gland were investigated using autopsy pituitaries as starting material. Beta-endorphin-related peptides were isolated from two batches of autopsy pituitaries (40 and 51 glands) by acid acetone extraction, acetone precipitation, gel filtration (Sephadex G-75 or Bio Gel P 4/P 10), cation exchange chromatography (SP-Sephadex C-25) and different types of reversed phase high performance liquid chromatography (RP-HPLC). Purification was monitored using beta-endorphin radioimmunoassay, which is specific to the 6-17 sequence of beta-endorphin. Methods suitable for microscale structural analyses of the isolated peptides were developed. Amino acid analysis was performed using quantitative precolumn dansylation and RP-HPLC separation of the dansyl amino-acids. Amino-terminal sequences were determined using semi-microscale manual Edman degradation. An RP-HPLC system was set up for sensitive and unambiguous identification of the released phenylthiohydantoin amino acids. The immunoreactive peptide with the highest apparent molecular weight was identified as human beta-lipotropin on the basis of its amino acid composition. The results of amino-terminal sequence analysis, amino acid compositions of the HPLC-isolated tryptic peptides and carboxy-terminal residue analysis were fully compatible with the previously suggested structure of human beta-lipotropin. About 20% of isolated pituitary beta-lipotropin appeared to be in deamidated form. No proteolytically degraded forms of beta-lipotropin were detected. The yield of pure beta-lipotropin was 6.7-7 nmol/gland. A peptide with properties similar to human beta-endorphin was isolated with a yield of 1.5-5 nmol/gland. Amino acid composition, amino-terminal sequence, carboxy-terminal residue and immunochemical properties were identical to those of human beta-endorphin as suggested previously. About 25% of beta-endorphin appeared to be in methionine sulphoxide form as isolated. Several minor components of immunoreactivity with molecular weight similar to beta-endorphin were detected but none of these were obtained pure even after three RP-HPLC purification steps. Further purification was impossible due to the scarcity of the starting material. A previously unidentified beta-endorphin-related peptide with an apparent molecular weight of about 2000 daltons was isolated from the autopsy pituitaries. Amino acid composition, amino-terminal residue, carboxy-terminal sequence and immunochemical properties showed the peptide to be beta-endorphin 1-18. The yield of isolated peptide was 0.4 nmol/gland. This peptide has not been pr

Amino Acid Sequence↗
PubMed2002

Regulation of cellular alpha-MSH and beta-endorphin during stimulated secretion from intermediate pituitary cells: involvement of aspartyl and cysteine proteases in the control of cellular levels of alpha-MSH and beta-endorphin.

The regulation of cellular levels of alpha-melanocyte stimulating factor (alpha-MSH) and beta-endorphin in response to stimulated secretion from intermediate pituitary cells in primary culture was investigated in this study. Regulation of the cell content of alpha-MSH and beta-endorphin occurred in two phases consisting of (a) initial depletion of cellular levels of these peptide hormones during short-term secretion (3 h) induced by isoproterenol, forskolin, or phorbol myristate acetate (PMA) which was followed by (b) long-term (24 h) increases in cellular levels of alpha-MSH and beta-endorphin in response to stimulated secretion induced by isoproterenol and PMA. In short-term experiments (3 h), cellular levels of alpha-MSH and beta-endorphin were reduced by 30-50% during stimulated secretion of these peptide hormones by isoproterenol (agonist for the beta-adrenergic receptor), forskolin that activates protein kinase A (PKA), and PMA that activates protein kinase C (PKC). Moreover, dopamine inhibited isoproterenol-induced depletion of cellular alpha-MSH and beta-endorphin. During long-term incubation of cells (24 h) with isoproterenol, cellular alpha-MSH and beta-endorphin were increased to twice that of controls (unstimulated cells). Treatment with PMA for 24 h also increased cellular levels of alpha-MSH and beta-endorphin. Moreover, cellular levels of alpha-MSH and beta-endorphin were decreased during long-term treatment of cells with an aspartyl protease inhibitor, pepstatin A, and with the cysteine protease inhibitor E64c. These results implicate aspartyl and cysteine proteases in the cellular production of alpha-MSH and beta-endorphin that requires proteolytic processing of their common precursor proopiomelanocortin (POMC). These findings demonstrate the parallel regulation of cellular levels of alpha-MSH and beta-endorphin during their cosecretion, which may involve aspartyl and cysteine proteases in the metabolism of these peptide hormones.

Animals↗
PubMed1984

Isolation and characterization of alpha-endorphin and gamma-endorphin from single human pituitary glands.

alpha-Endorphin and gamma-endorphin, two closely related peptides of the pro-opiomelanocortin family with characteristic biological activities, were purified to homogeneity from single human pituitary glands and chemically identified. Isolation of the peptides was based on size fractionation by Sephadex G-75 chromatography followed by two HPLC steps using reverse-phase and paired-ion reverse-phase systems and was monitored by radioimmunoassay. During the isolation procedure alpha- and gamma-endorphin-sized material behaved chromatographically and immunologically indistinguishably from synthetic alpha- and gamma-endorphin. The amino acid composition and NH2-terminus of isolated peptides demonstrated their identity as authentic alpha-endorphin and gamma-endorphin. Acetylated forms were absent. In addition, evidence is provided that large forms with alpha- and gamma-endorphin immunoreactivity detected during gel filtration are human lipotropin-(1-74) and -(1-75), respectively. The data substantiate that alpha-endorphin and gamma-endorphin exist as endogenous peptides in the human pituitary gland.

Amino Acids↗
PubMed1982

Non-opiate beta-endorphin fragments and dopamine-V. gamma-Type endorphins and prolactin secretion in rats.

The effects on prolactin secretion of three peptide-derivatives of beta-endorphin which show neuroleptic-like activities in rats were studied. Intravenous administration of gamma-endorphin (beta-endorphin (beta E) 1-17) enhanced plasma prolactin levels. Gamma-Endorphin did not affect the prolactin secretion by hemipituitary glands incubated in vitro and by cultured pituitary cells, but it reversed, in a dose-dependent way, the dopamine-induced inhibition of prolactin release. This effect of gamma-endorphin could be prevented by co-incubation with the opiate-antagonist naloxone. In vivo studies with non-opiate-like fragments of gamma-endorphin, des-Tyr1-gamma-endorphin (DT gamma E, beta E 2-17) and des-enkephalin-gamma-endorphin (DE gamma E, beta E 6-17), showed that these peptides suppressed the plasma prolactin levels, when prolactin release was slightly stimulated. However, DE gamma E dose-dependently enhanced plasma prolactin levels, when prolactin release was low. Subchronic treatment with DE gamma E for 4 days made prolactin release more sensitive to the inhibitory action of small doses of apomorphine. Neither DT gamma E nor DE gamma E affected prolactin release by hemipituitary glands and cultured pituitary cells. They did also not affect the dopamine-induced inhibition of prolactin release in vitro. It is suggested that gamma-endorphin increases prolactin secretion by interfering with dopaminergic systems in the pituitary and that DT gamma E and DE gamma E have a modulatory action on prolactin secretion.

Animals↗
PubMed1981

Proteolytic conversion of beta-endorphin by brain synaptic membranes. Characterization of generated beta-endorphin fragments and proposed metabolic pathway.

This study concerned the fragmentation of beta-endorphin (beta-EP-(1-31) by synaptic membrane-bound peptidases. The peptides which accumulated during digestion of beta-endorphin by isolated synaptosomal plasma membrane preparations of rat brain were separated and isolated by high pressure liquid chromatography. Amino acid analysis of the peptide fractions indicated the formation of beta-EP-(1-21), beta-EP-(2-21) (pH 7.4), beta-EP-(18-31), beta-EP-(1-14), and beta-EP-(1-13) (pH 5.0) in addition to previously identified gamma-endorphin (beta-EP-(1-17)), alpha-endorphin (beta-EP-(1-16), and their des-tyrosine fragments (Burbach, J. P. H., Loeber, J. G., Verhoef, J., Wiegant, V. M., De Kloet, E. R., and De Wied, D. (1980) Nature 283, 96-97). The beta-endorphin fragments obtained with crude or with purified synaptosomal plasma membranes differed only quantitatively. The peptidase which converted gamma-endorphin into beta-EP-(1-16), beta-EP-(1-15), beta-EP-(1-14), and beta-EP-(1-13), was considerably active at pH 5.0 and resembled carboxypeptidase A in degrading gamma-endorphin; the activity was reduced by the carboxypeptidase A inhibitor D-phenylalanine. The data supplement previous findings and allow routes to be delineated for the conversion of beta-endorphin by brain synaptic membranes. A pathway comprising the main events in the conversion processes is proposed and is discussed in relationship to the significance of beta-endorphin as a precursor for neuropeptides with distinct central activities.

Amino Acid Sequence↗
PubMed1991

Synthesis and receptor binding activity of elephant beta-endorphin, a beta-endorphin homolog with highly potent analgesic activity.

Elephant beta-endorphin and its analog, elephant beta-endorphin(6-31) were synthesized by standard solid phase method. Receptor binding activity showed that elephant beta-endorphin was five to six times more potent than human beta-endorphin in its ability to bind to opiate receptors on rat brain membrane. In a previous study (Wong, C.-L., Wai, M.-K., Cheng, H.-C., Chung, D. & Yamashiro, D (1990) Clinical and Experimental Pharmacology and Physiology 16, 33-37), tail flick test for intracerebroventricularly administered beta-endorphin showed that the antinociceptive potency of elephant beta-endorphin was seven to eight times higher than that of human beta-endorphin in mice. Results from both studies suggest that elephant beta-endorphin was a much more potent antinociceptive agent than human beta-endorphin in tail flick test and its higher analgesic activity might be due to its higher affinity for opiate receptors in the brain.

Amino Acid Sequence↗
PubMed1993

Topography and characteristics of specific binding sites for non-opioid gamma-type endorphins in the rat brain as studied by autoradiography with [35S]Met-desenkephalin-gamma-endorphin.

An in vitro autoradiographic study was performed to characterize specific rat brain binding sites for non-opioid neuroleptic-like gamma-type endorphins, using [35S]Met-des-enkephalin-gamma-endorphin ([35S]Met-DE gamma E; [35]S-beta-endorphins(5-17)) with high specific activity as radioligand. The binding sites appeared to be confined to rat forebrain regions, e.g., orbital cortex, frontal cortex, cingulate cortex, piriform cortex, nucleus accumbens, amygdala, mediodorsal nucleus of the thalamus and arcuate and periventricular nuclei of the hypothalamus. These regions are part of the mesocorticolimbic feedback circuit. Densitometric analysis of the autoradiographs revealed that the density of the binding sites was highest in the mediodorsal nucleus of the thalamus and the amygdala. Concentration-dependent displacement of [35S]Met-DE gamma E (500 pM) with DE gamma E yielded an IC50 of 0.6 nM whereas DE alpha E (beta-endorphin(6-16)) had an IC50 of 210 nM. Various endorphins, sharing the gamma-endorphin C terminus, displaced [35S]Met-DE gamma E to the same extent as non-labelled DE gamma E (at 10(-6) M) whereas non-endorphin peptides did not show displacing capacity. Possible relationships of the binding sites with opioid receptors were investigated. DAMGO (mu) and DPDPE (delta) displaced [35S]Met-DE gamma E to some extent at 10(-6) M whereas U69,593 (kappa) was inactive, suggesting that the binding sites for gamma-type endorphins may resemble mu- and delta-opioid receptors in some aspects. Similarly, relationships with dopamine receptors were investigated. Haloperidol partially displaced [35S]Met-DE gamma E whereas sulpiride, SKF38,393 and 3-PPP at 10(-6) M did not induce significant displacement. Thus, binding sites are distinct from dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1982

Identification of beta-endorphin-6(16-17) as the principal metabolite of des-tyrosin-gamma-endorphin (DTgammaE) in vitro and assessment of its activity in neurotransmitter receptor binding assays.

Des-tyrosine-gamma-endorphin (beta-endorphin-(2-17); DTgamma E) lacks direct in vitro activity at dopaminergic receptors, but does inhibit in vivo [3H]spiperone binding in various rat brain areas. The principal objective of these studies was to test the hypothesis that DTgammaE may exert its selective, neuroleptic-like activity through an active metabolite. Accordingly, DTgammaE was incubated at 37 degrees C in a whole rat brain homogenate of neutral pH after which samples were prepared for HPLC analysis. The major, heat-stable metabolite of DTgammaE was identified as the clinically active, beta-endorphin related fragment, beta-endorphine-(6-17). The beta-endorphin sequences 4-17, 5-17, l0-17, 12-17 and 2-16 were also present but in minor amounts. Identical results were obtained studying DTgammaE metabolism using rat striatal tissue slices. Neurotransmitter receptor binding experiments showed that beta-endorphin-(6-17) was inactive at central dopaminergic, serotonergic, muscarinic, benzodiazepine and opiate receptors measured in vitro. Thus, like DTgammaE, beta-endorphin-(6-17) differs from classical neuroleptics in that it does not inhibit in vitro [3H]spiperone binding in the corpus striatum, frontal cortex or mesolimbic areas of the rat brain. It may be that DTgammaE and beta-endorphine-(66-17) exert their selective neuroleptic-like activity through an indirect inhibition of central dopaminergic activity, possibly in combination with an in vivo antagonism of the postsynaptic dopamine receptor.

Animals↗
PubMed1982

Non-opiate beta-endorphin fragments and dopamine-IV. gamma-Type endorphins may control dopaminergic systems in the nucleus accumbens.

Chronic treatment with des-enkephalin-gamma-endorphin (DE gamma E, beta-endorphin 6-17) twice daily for 10 days into the nucleus accumbens of rats resulted in hypoactivity, while similar treatment with gamma-endorphin antiserum led to a marked hyperactivity. This enhanced activity persisted for at least 3 days following discontinuation of treatment. Rats chronically treated with gamma-endorphin antiserum into the nucleus accumbens habituated at a slower rate when tested repeatedly for locomotor activity, as well as for nociception. Passive avoidance behaviour was attenuated in the treated rats, when they were trained during treatment, but not when the learning trial was given before treatment and testing was performed during treatment. Treatment with gamma-endorphin antiserum did not affect the diurnal rhythm in locomotion, the responsiveness to nociceptive stimulation and the basal and novelty stress induced-plasma corticosteroid levels. It is concluded that chronic treatment with gamma-endorphin antiserum into the nucleus accumbens, which may lead to bio-inactivation of gamma-type endorphins, causes hyperactivity and disturbances in habituation and cognitive functions. It is suggested that gamma-type endorphins are physiologically involved in the control of distinct dopaminergic systems in the nucleus accumbens. The findings are discussed in relation to the role of mesolimbic dopaminergic systems in schizophrenic psychosis.

Animals↗
PubMed1986

beta-Endorphin-(1-27) inhibits the spinal beta-endorphin-induced release of Met-enkephalin.

The effect of intraventricular beta-endorphin-(1-27) on the spinal release of Met-enkephalin induced by intraventricular beta-endorphin was studied using the intrathecal superfusion technique in urethane anesthetized rats. Intraventricular injection of beta-endorphin at a dose of 15 micrograms released Met-enkephalin from the spinal cord. This release of Met-enkephalin induced by beta-endorphin was significantly reduced by beta-endorphin-(1-27), 60 micrograms, injected intraventricularly. Injection of beta-endorphin (1-27) itself did not cause any release of Met-enkephalin. The finding is in line with the previous report that beta-endorphin (1-27) inhibited the analgesia induced by beta-endorphin.

Animals↗
PubMed1981

beta-Endorphin-induced stimulation of central sympathetic outflow: beta-endorphin increases plasma concentrations of epinephrine, norepinephrine, and dopamine in rats.

Intracisternal administration of synthetic human beta-endorphin (0.058-7.25 nmol) in chronically cannulated, conscious, freely moving, adult male rats increased plasma concentrations of epinephrine, norepinephrine, and dopamine in a dose-related manner. Epinephrine secretion was the most sensitive to the stimulatory effect of intracerebral beta-endorphin; plasma epinephrine increased transiently in response to 0.058 nmol. Of the three catecholamines, plasma epinephrine showed the greatest and most rapid response to the largest dose (7.25 nmol) studied. Plasma norepinephrine increased significantly in response to 1.45 nmol, peaking later than plasma epinephrine. Plasma dopamine increased only in response to the highest dose examined. These beta-endorphin effects on plasma catecholamines were inhibited by intraarterial naloxone (1.1 mumol/kg), supporting mediation at opioid receptors. Pretreatment with the ganglionic blocking agent chlorisondamine inhibited the responses of all three catecholamines to intracisternal beta-endorphin. Bilateral adrenal denervation completely prevented the plasma epinephrine response to beta-endorphin and blunted the plasma norepinephrine and dopamine responses. Prior intracisternal administration of hemicholinium-3 blocked the plasma responses of all three catecholamines to intracisternal beta-endorphin, providing evidence for the involvement of central cholinergic neurons in the mechanism mediating beta-endorphin-induced increases in plasma catecholamines. The data are consistent with the hypothesis that endorphins act at a presently unknown brain site(s) to increase the central sympathetic outflow to adrenal medulla and peripheral sympathetic nerve endings, thus stimulating peripheral catecholamine release and increasing plasma concentrations of epinephrine, norepinephrine, and dopamine.

Animals↗
PubMed1989

Identification of the beta-endorphin-binding subunit of the SC5b-9 complement complex: S protein exhibits specific beta-endorphin-binding sites upon complex formation with complement proteins.

Beta-Endorphin has been reported to specifically interact with SC5b-9 complement complexes via non-opioid binding sites. Covalent cross-linking of [125I]beta H-endorphin to SC5b-9 and analysis of the cross-linking products by gel electrophoresis and subsequent autoradiography revealed a single specifically labelled species which was identical with the S protein subunit of the complement complex. In contrast to SC5b-9, no cross-linking of labelled beta-endorphin to subunits of C5b-9(m) could be observed, indicating that beta-endorphin binding to SC5b-9 was mediated exclusively via S protein. Beta-Endorphin binding to SC5b-9 was compared with binding to purified S protein. Whereas beta-endorphin binding to purified S protein was only modest, complex formation of S protein with complement proteins led to a strong increase in beta-endorphin-binding site concentration, compatible with the exposure of primarily cryptic beta-endorphin-binding sites on S protein.

Binding, Competitive↗
PubMed2003

Occurrence of beta-endorphin binding sites in the pituitary of the frog Rana esculenta: effect of beta-endorphin on luteinizing hormone secretion.

The possible effect of proopiomelanocortin-derived peptide, beta-endorphin on frog gonadotrope cells was investigated. Binding and internalization of beta-endorphin to pituitary pars distalis cultured cells were visualized by immunofluorescence and analyzed by means of confocal laser scanning microscopy. Using biotinylated endorphin, the time-course of beta-binding showed that this opioid was internalized through receptor-mediated endocytosis, the mechanism in which actin and clathrin were involved; then, the lysosomal degradation program occurred at later stages. The beta-endorphin binding was well antagonized by Naloxone, the opiate receptor antagonist, and up-regulated since more rapid response was obtained in the previously primed cells. The double immunostaining reaction for beta-endorphin and LH beta-subunit revealed that half the beta-endorphin labeled cell population was positively immunostained for LH beta-subunit, and beta-endorphin was able to induce an increasing trend of LH secretion in cultured pars distalis cells. Therefore, it seems that beta-endorphin acts directly on pituitary pars distalis and influences gonadotropin secretion through the interaction with its own receptor.

Actins↗
PubMed1982

beta-Endorphin proteolysis by guinea-pig ileum myenteric plexus membranes: increased gamma-endorphin turnover after chronic exposure to morphine.

The influence of chronic morphine exposure in vitro on the biotransformation of beta-endorphin (beta E) was investigated using the myenteric plexus-longitudinal muscle of guinea-pig ileum. A membrane preparation was incubated with beta E and the degradation of beta E as well as the accumulation of several beta E fragments in the incubation medium were followed with time. The levels of peptides were determined by specific radioimmunoassays after separation by high-pressure liquid chromatography. It was found that exposure to morphine did not affect the disappearance of beta E, but altered the time course of accumulation of beta E fragments. In fact, the accumulation of gamma-endorphin, alpha-endorphin and des-tyrosine1-alpha-endorphin was enhanced, while that of des-tyrosine1-gamma-endorphin was not change. Additionally, the disappearance of gamma-endorphin appeared to be stimulated by morphine exposure. These data provide evidence that the fragmentation of beta E is changed by chronic morphine exposure in such a way that the turnover of gamma-endorphin is increased.

Animals↗
PubMed1983

Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphin with ACTH or epinephrine on memory consolidation.

The effect on retention of the post-training intraperitoneal administration of ACTH1-24 (0.2 or 2.0 micrograms/kg), epinephrine HCl (5.0 or 50.0 micrograms/kg), human beta-endorphin (0.1 or 1.0 microgram/kg), naloxone (0.4 mg/kg), and of the combination of naloxone or beta-endorphin with ACTH or epinephrine was studied in two different but closely related step-down inhibitory avoidance tasks in rats: task 1 (5 cm high 25 X 25 cm platform; 0.5 mA continuous footshock) and task 2 (7 X 25 cm platform, 0.3 mA discontinuous footshock). In task 1, saline control animals showed good retention in a test session carried out 24 hr later; beta-endorphin, ACTH and epinephrine caused amnesia; beta-endorphin potentiated the amnesic effect of ACTH and epinephrine; and naloxone caused memory facilitation and reversed the amnesic effect of ACTH and epinephrine. In task 2, control animals showed poor retention; beta-endorphin caused amnesia at the dose of 0.1 but not 1.0 microgram/kg; the other three drugs caused memory facilitation; naloxone potentiated the facilitatory effect of ACTH and epinephrine; and beta-endorphin reversed it and transformed it into a deep amnesia. These findings suggest that an opioid-mediated amnesic mechanism modulates the effect of ACTH and epinephrine on memory consolidation, either by dampening that effect when training parameters tend to make it facilitatory, or by enhancing it when training conditions tend to make it amnesic. On the basis of these and previous data it seems likely that the amnesic effect of ACTH and epinephrine could be mediated by endogenous beta-endorphin release.

Adrenocorticotropic Hormone↗
PubMed1984

beta-endorphin-(1-27) is an antagonist of beta-endorphin analgesia.

beta h-Endorphin-(1-27), a naturally occurring fragment of human beta-endorphin (beta h-endorphin), diminishes the analgesic effect of beta h-endorphin when coinjected intra-cerebroventricularly into mice. A parallel shift in the dose-response curve of beta h-endorphin in the presence of beta h-endorphin-(1-27) suggests competition at the same site. The potency of beta h-endorphin-(1-27) in antagonizing analgesia is greater than 4 times greater than that of the opiate antagonist naloxone.

Analgesia↗
PubMed1981

beta-Endorphin 61-91 and other beta-endorphin-immunoreactive peptides in human semen.

Human semen contains large amounts of authentic beta-endorphin and other beta-endorphin immunoreactive peptides. To eliminate the non-specific effects of semen in the beta-endorphin RIA, the beta-endorphin immunoreactive peptides were extracted with octadecylsilane-C18 reverse phase beads. beta-Endorphin immunoreactivity was parallel to the RIA standard curve. Sephadex G-50 gel chromatography showed that 93% of the immunoreactive material coeluted with beta-endorphin. Reversed phase high pressure liquid chromatography of semen extract demonstrated several peaks of beta-endorphin immunoreactivity; one of these was coincident with synthetic h-beta-endorphin61-91.

Chromatography, Gel↗