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)

Chromaffin granules, the secretory organelles of the neuron-like adrenal medullary chromaffin cells, have previously been shown to store and liberate neurotrophic activities that support in vitro survival of several neuron populations including those innervating the adrenal medulla. Molecules resembling fibroblast growth factor and ciliary neurotrophic factor have been identified among these activities. Since chromaffin granules store a variety of neuropeptides and many neuropeptides can have pleiotropic effects on neuronal growth and maintenance we have tested 24 different neuropeptides for their capacities to promote survival of embryonic chick ciliary, dorsal root and sympathetic ganglionic neurons. Peptides tested included several derivatives of proenkephalin (Leu- and met-enkephalin, fragments BAM 22, B, F and E), somatostatin, substance P, neuropeptide Y, neurotensin, VIP, bombesin, secretin, pancreastatin, dynorphin B, dynorphin 1-13, beta-endorphin, alpha-, beta-, and gamma-MSH. Control cultures received saturating concentrations of ciliary neurotrophic or nerve growth factor (CNTF; NGF), or no trophic supplements. At 1 x 10(-5) M leu- and met-enkephalin as well as somatostatin supported sympathetic neurons to the same extent as NGF. At the same concentrations, leu-enkephalin, the proenkephalin fragments BAM 22 and E, and somatostatin maintained about half of the dorsal root ganglionic neurons supported by NGF, but were not effective on ciliary neurons. VIP promoted the survival of approximately 50% of the ciliary and embryonic day 10 dorsal root ganglionic neurons as compared to saturating amounts of CNTF, but required the presence of non-neuronal cells in the cultures to be effective. Neurotensin (1 x 10(-5) M had a small effect on ciliary neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Screening of adrenal medullary neuropeptides for putative neurotrophic effects. 163 76

Binding of the stable melanocortin(4-9) analogue, Org2766 [Met(O2)-Glu-His-Phe-D-Lys-Phe] to cultured rat sciatic nerve Schwann cells was demonstrated using a biotinylated derivative in semiquantitative histochemical and CELISA assays. Org2766 bound to Schwann cells, but not to fibroblasts, and was displaced maximally by unlabeled Org2766, alpha-MSH and ACTH(1-24). Displacement of Org2766 from the binding sites was considerably reduced by N- and C-truncation of the peptide. Specific binding of Org2766 was also demonstrated in the immortal rat Schwann cell line SCL4.1/F7 and was more pronounced in cells displaying a differentiated morphology. Org2766 and alpha-MSH increased cyclic AMP content of Schwann cells but neither stimulated DNA synthesis when applied alone. However, in the presence of a priming (subthreshold) concentration of the mitogen, cholera toxin, Org2766 and alpha-MSH caused a delayed increase in DNA synthesis. Org2766 did not modulate the expression of several differentiation-related Schwann cell markers. However, Org2766 increased immunoreactivity for p75 low-affinity NGF receptor on Schwann cells and evoked the release of neurotrophic factor(s) that synergized with NGF in stimulating neurite outgrowth in rat DRG neurons. The results indicate that Schwann cells are a primary target for the action of Org2766 and provide evidence for an indirect mechanism by which melanocortins might stimulate neurite sprouting in regenerating peripheral nerve axons.
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PMID:Melanocortin analogue Org2766 binds to rat Schwann cells, upregulates NGF low-affinity receptor p75, and releases neurotrophic activity. 765 7

A pheochromocytoma from a 59-year-old woman was found to be immunoreactive to adrenocorticotropin (ACTH), chromogranin, neurofilament-200, neuron-specific enolase and S-100 protein. Northern blot analysis showed that both proopiomelanocortin (POMC) and corticotropin-releasing hormone (CRH) genes were expressed in the pheochromocytoma but not in the surrounding adrenal cortex. In primary culture, the POMC and CRH mRNAs were increased by dexamethasone (500 micrograms/l for 3 days) up to 10- and 15-fold of the control, respectively. The secretion of ACTH also was stimulated eightfold with the same treatment. The stimulatory effect of dexamethasone on POMC gene expression was inhibited 70% by nerve growth factor (NGF, 200 micrograms/l), 30% by 12-O-tetradecanoyl phorbol 13-acetate (TPA, 160 nmol/l) (a protein kinase-C activator) and 30% by (Bu)2cAMP (1 mmol/l). On the other hand, NGF alone increased the CRH mRNA accumulation up to 10-fold, and further enhanced the stimulatory effect of dexamethasone on the CRH mRNA twofold, and TPA inhibited (30%) the dexamethasone-induced CRH mRNA accumulation. Furthermore, the conditioned medium of the pheochromocytoma cells increased secretion of corticosterone fourfold in the primary culture of rat fetal adrenal cells. Our results indicate abnormal expression and regulation of POMC and CRH genes in this pheochromocytoma.
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PMID:Pheochromocytoma expressing adrenocorticotropin and corticotropin-releasing hormone; regulation by glucocorticoids and nerve growth factor. 792 Dec 4

Mitotically active Schwann cells isolated from adult rat sciatic nerve segments were cultivated, using a bivariate BrdU/DNA flow cytometry analysis, to test the effect of b-FGF (10 ng/ml), alpha-MSH (10 ng/ml), NGF (10 ng/ml), PDGF-AB (10 ng/ml), and TGF-beta 1 (10 ng/ml) on the cell cycle. Compared to control or cholera toxin-treated cultures, no significant differences (P < 0.05; Newmann-Keuls test) were observed in the proportion of G0G1 cells, S cells, G2M cells, and in the LI when alpha-MSH, NGF, PDGF-AB, or TGF-beta 1 were present. The S phase duration varied from 6.16 +/- 0.24 to 7.86 +/- 2.6 h, and the deduced potential doubling time was estimated at between 46.70 +/- 7.09 and 56.05 +/- 7.55 h. In contrast, when b-FGF was added to the culture, the cell cycle was significantly modified, and the proportion of G0G1 cells decreased from 68-77% to 59-64%, while the proportion of S cells increased from 14-16% to 24.0-26.4%. Although S phase duration was not significantly changed (6.02 +/- 0.36 h), the 1.7- to 2.8-fold LI increase reduced the potential doubling time to 25.99 +/- 6.13 h. We conclude from these results that only b-FGF-induced adult rat Schwann cells dramatically reenter in cell cycle and that this growth factor may be an axonally derived signal-promoting mitogenesis after nerve injury.
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PMID:Establishment of adult rat Schwann cell cultures: effect of b-FGF, alpha-MSH, NGF, PDGF, and TGF-beta on cell cycle. 792 48

Work in the past 8 years, particularly in the past 1-2 years, has greatly expanded our understanding of the mechanisms by which ultraviolet irradiation stimulates melanogenesis in the skin. A direct effect of UV photons on DNA results in up-regulation of the gene for tyrosinase, the rate-limiting enzyme in melanin synthesis, as well as an increase in cell surface expression of receptors for at least one of the several known keratinocyte-derived melanogenic factors, MSH. Direct effects of UV on melanocyte membranes, releasing DAG and arachidonic acid, may also play a role in the tanning response. Diacylglycerol may activate PKC-beta, which in turn phosphorylates and activates tyrosinase protein; the pathways by which products of other inflammatory mediator cascades may act on melanogenesis are unknown. The tanning response also relies heavily on UV-stimulated increased production and release of numerous keratinocyte-derived factors including bFGF, NGF, endothelin-1 and the POMC-derived peptides MSH, ACTH, beta-LPH and beta-endorphin. These factors variably induce melanocyte mitosis, increase melanogenesis, enhance dendricity and prevent apoptotic cell death following the UV injury. Thus, events within the epidermal melanin unit conspire to maintain or increase melanocyte number, increase melanin pigment throughout the epidermis. Overall, ultraviolet-induced melanogenesis may be one part of a eukaryotic SOS response to damaging ultraviolet irradiation that has evolved over time to provide a protective tan in skin at risk of further injury from sun exposure. These recent insights into the mechanisms underlying ultraviolet-induced melanogenesis offer the opportunity for novel therapeutic approaches to minimizing acute and chronic photodamage in human skin.
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PMID:Mechanisms of ultraviolet light-induced pigmentation. 857 60

1. The modulator effects of a series of neurotransmitters and related substances were tested on responses to adenosine 5'-triphosphate (ATP) at a recombinant P2x2 receptor expressed in defolliculated Xenopus oocytes. 2. Nicotine, 5'-hydroxytryptamine (5-HT), noradrenaline, adenosine, bradykinin and histamine (all 100 microM) potentiated the responses to ATP (3 microM). an effect found due to acidification of the bathing solution by these drugs. 3. Arachidonic acid, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP) (all 100 microM) and nerve growth factor (NGF; 50 ng ml-1) potentiated the responses to ATP (3 microM) through a largely or wholly pH-independent effect. 4. Small acidic and alkaline shifts, as little as 0.03 pH-units, enhanced or diminished the responses to ATP, respectively. A linear relationship existed between the degree of potentiation of the ATP-induced responses caused by nicotine, 5-HT, noradrenaline, adenosine, bradykinin and histamine and the potentiation of these responses induced by the addition of acid to the superfusate. 5. Since P2x receptors on sensory neurones include P2x2 subunits, the attendant acidosis and ATP-release associated with tissue injury may play a role in sensitizing sensory nerve fibres.
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PMID:Potentiation of ATP-responses at a recombinant P2x2 receptor by neurotransmitters and related substances. 911 13

The comparison of distinct cell-differentiation models can help to answer the question whether there are common signalling pathways activated in the cells during the differentiation process or not. The differentiation of PC12 pheochromocytoma cells in response to NGF, the differentiation of melanoma B16 cells triggered by alpha-MSH, the formation of myotubes by L6E9 skeletal muscle myoblasts deprived of FCS or differentiation of HL-60 cells in response to steroid hormone 1,25-dihydroxyvitamin D3 share some similarities in the activation of signal transduction pathways. Differentiation-inducing agents stimulate sustained activation and nuclear translocation of MAP kinases (ERK1 and ERK2). Some of differentiation-inducing agents activate PI3-kinase as well, and the inhibition of the PI3K/p70S6K pathway blocks the process of differentiation in the cells.
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PMID:[Does the universal "signal transduction pathway of differentiation" exist? Comparison of different cell differentiation experimental models with differentiation of HL-60 cells in response to 1,25-dihydroxyvitamin D3]. 1035 95

The various components of the endocannabinoid system were discovered in the last twenty years. The cannabinoid system has attracted pharmacologists interest for its potential as therapeutic targets for several diseases ranging from obesity to Parkinson's disease and from multiple sclerosis to pain. Research initially focused on cannabinoid receptor 1 (CB1), but, due to psychotropic side effects related to its activation, the attempts to develop an agonist drug for this receptor has been so far unsuccessful. Recently the possibility to target CB2 has emerged as an alternative for the treatment of pain. The main advantage of targeting CB2 resides in the possibility to elicit the analgesic effect without the psychotropic side effects. Evidence of the analgesic effect of CB2 selective agonists has been obtained in various models of both inflammatory and neuropathic chronic pain. To explain the mechanism at the basis of this analgesic effect different hypotheses have been proposed: effect on inflammatory cells, reduction of basal NGF tone, induction of beta-endorphin release from keratinocytes, direct action on nociceptors. Evidence in support of this last hypothesis comes from down regulation of capsaicin-induced CGRP release in spinal cord slices and Dorsal Root Ganglia (DRG) neurons in culture after treatment with CB2 selective agonists. CB2 agonists are probably acting through several mechanisms and thus CB2 represents an interesting and promising target in the chronic pain field. Further clarification of the mechanisms at the basis of CB2 analgesic effect would surely be an intriguing and stimulating area of research for the years to come.
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PMID:[The cannabinoid system and pain: towards new drugs?]. 1935 15