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)

Corticotropin-releasing factor (CRF) is the most potent and effective natural stimulant of corticotropin (ACTH) secretion. In a tumor cell line of the mouse anterior pituitary (AtT-20/D16-16) consisting of a homogeneous population of corticotrophs, CRF is known to increase adenylate cyclase and cAMP-dependent protein kinase activities as well as to release ACTH. To determine whether activation of cAMP-dependent protein kinase is essential for CRF to evoke the secretion of ACTH, an inhibitor (PKI) of this kinase was inserted into AtT-20 cells. This was accomplished by first encapsulating PKI into liposomes and then covalently coupling them to protein A for binding to antibodies directed against an AtT-20 cell surface antigen, N-CAM (neural cell adhesion molecule). The binding of the liposomes to the anti-N-CAM antibodies led to the internalization of the PKI into the tumor cells. The PKI treatment greatly attenuated CRF-stimulated ACTH release as well as the secretory response to beta-adrenergic agonists. However, ACTH release in response to caerulein, an agonist of cholecystokinin 8 receptors, was not altered by the PKI treatment. CRF treatment also increased the levels of mRNA for proopiomelanocortin (POMC), the precursor for ACTH in AtT-20 cells. Application of liposomes containing PKI to AtT-20 cells blocked the ability of CRF and 8-bromo-cAMP, but not phorbol ester, to increase POMC mRNA levels. The results revealed an essential role for cAMP in mediating the effect of CRF on ACTH release and POMC gene expression.
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PMID:Corticotropin-releasing factor-induced adrenocorticotropin hormone release and synthesis is blocked by incorporation of the inhibitor of cyclic AMP-dependent protein kinase into anterior pituitary tumor cells by liposomes. 299 99

Insertion of a crude preparation of cyclic AMP (cAMP)-dependent protein kinase inhibitor (PKI) into a cloned mouse anterior pituitary cell line (AtT-20/D16-16) blocked cAMP-mediated hormone release. This was accomplished by developing a technique to incorporate PKI into multicellular cultures. The technique involved the encapsulation of the PKI into liposomes coupled to Protein A (a bacterial protein that binds to the Fc portion of antibodies). Application of such liposomes to AtT-20 cells targeted by pre-treatment with an antiserum against neural cell adhesion molecule (a cell surface glycoprotein expressed by these cells) resulted in the attachment of the liposomes onto the cell surface followed by the delivery of the liposome content into the cells. The AtT-20 cells respond to cAMP-promoting agents such as forskolin by secreting the hormone adrenocorticotropin (ACTH). Liposomes containing PKI and coupled to protein A specifically blocked cAMP-mediated ACTH release from cells treated with anti-N-CAM antibodies. In contrast, the ACTH release response to K+ or phorbol esters does not appear to involve cAMP and was not reduced by such manipulations. The specificity of PKI to block hormone release initiated by one but not by other secretagogues directly links cAMP-dependent protein kinase with the ACTH release process but suggests that there are other mechanisms also involved in stimulus-secretion coupling in corticotrophs.
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PMID:Liposome delivery of cyclic AMP-dependent protein kinase inhibitor into intact cells: specific blockade of cyclic AMP-mediated adrenocorticotropin release from mouse anterior pituitary tumor cells. 300 90

A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using non-MHC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral blood lymphocytes were selected by immobilization with anti-CD3 monoclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-six outpatients with cancer whose performance status were over 80% on Karnofsky scale were selected for this study. About 6 x 10(9) BAK cells were returned by intravenous drip infusion, at one month intervals at an outpatient clinic to each of 20 advanced cancer patients in whom many metastatic lesions were found postoperatively, and to 6 patients with no postoperatively detectable metastases. The proportion of CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells have strong cytotoxic activity and produced 20 ng/10(9) cells of beta-endorphin, an intracerebral hormone. During the course of BAK therapy, we adopted the Face scale as a QOL indicator. The QOL of all patients remained satisfactory or improved. Beta-endorphin is thought to make patients feel well and maintains good QOL because of its potent analgesic, sedative activity. From that facts that CD56 is a neural cell adhesion molecule and a member of the Ig superfamily, and that the CD56-positive cell produces beta-endorphin, we concluded that the CD56-positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell. Administration of BAK cells allowed all 20 advanced cancer patients with metastases to survive for over one year. All 6 patients receiving the same therapy for prevention of postoperative metastasis have been recurrence-free for one to five years.
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PMID:Effector mechanism and clinical response of BAK (BRM-activated killer) immuno-cell therapy for maintaining satisfactory QOL of advanced cancer patients utilizing CD56-positive NIE (neuro-immune-endocrine) cells. 1147 30

The annual reproductive cycle in sheep may reflect a functional remodeling within the GnRH system. Specifically, changes in total synaptic input and association with the polysialylated form of neural cell adhesion molecule have been observed. Whether seasonal changes in a specific subset(s) of GnRH inputs occur or whether glial cells specifically play a role in this remodeling is not clear. We therefore examined GnRH neurons of breeding season (BS) and nonbreeding season (anestrus) ewes and tested the hypotheses that specific (i.e. gamma-aminobutyric acid, catecholamine, neuropeptide Y, or beta-endorphin) inputs to GnRH neurons change seasonally, and concomitant with any changes in neural inputs is a change in glial apposition. Using triple-label immunofluorescent visualization of GnRH, glial acidic fibrillary protein and neuromodulator/neural terminal markers combined with confocal microscopy and optical sectioning techniques, we confirmed that total numbers of neural inputs to GnRH neurons vary with season and demonstrated that specific inputs contribute to these overall changes. Specifically, neuropeptide Y and gamma-aminobutyric acid inputs to GnRH neurons increased during BS and beta-endorphin inputs were greater during either anestrus (GnRH somas) or BS (GnRH dendrites). Associated with the changes in GnRH inputs were seasonal changes in glial apposition, glial acidic fibrillary protein density, and the thickness of glial fibrils. These findings are interpreted to suggest an increase in net stimulatory inputs to GnRH neurons during the BS contributes to the seasonal changes in GnRH neurosecretion and that this increased innervation is perhaps stabilized by glial processes.
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PMID:Seasonal plasticity within the gonadotropin-releasing hormone (GnRH) system of the ewe: changes in identified GnRH inputs and glial association. 1286 49

Morphological plasticity has been demonstrated between breeding and anestrous seasons in the ewe hypothalamus, particularly for the gonadotropin-releasing hormone (GnRH) system. We sought to determine the impact of a photoperiodic transition, from long days (LD, 16 h light/24 h) to short days (SD; 8 h light/24 h), on the association between a marker of cerebral plasticity, the polysialylated form of neural cell adhesion molecule (PSA-NCAM), and two diencephalic populations: the GnRH and beta-endorphin (beta-END) neurons, the latter being potent inhibitors of GnRH neuronal activity. We also estimated the number of contacts on GnRH neurons after the passage to SD, using synaptophysin as a marker for synaptic buttons. Those parameters were evaluated in ovariectomized estradiol-replaced ewes using double immunocytochemistry and confocal microscopy at different times after the transition to SD: day 0 (D0), D30, D45, D60 and D112. Luteinizing hormone (LH) secretion was recorded throughout the experiment. High LH levels were observed only at D112. Significantly more PSA-NCAM was found in the GnRH neuron perimeters in the D112 group than in the other groups. This increase was not associated with any change in the number of synaptophysin-immunoreactive contacts on GnRH neurons. The beta-END peri-neuronal space was affected negatively by the transition to SD: the percentage of PSA-NCAM on beta-END neurons decreased between D45 and D112 in the posterior two thirds of the arcuate nucleus (ARC). These results suggest that photoperiod may reorganize cell interactions in different hypothalamic areas, ultimately reactivating GnRH neurons, in our model of ovariectomized-estradiol replaced ewes.
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PMID:Relationship between polysialylated neural cell adhesion molecule and beta-endorphin- or gonadotropin releasing hormone-containing neurons during activation of the gonadotrope axis in short daylength in the ewe. 2058 Sep 21