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)

We have examined the effects of a biologically active tumor promoting phorbol ester (phorbol 12-myristate, 13-acetate (PMA] which activates protein kinase C (PKC) on melanotropin receptor function and cell growth in the M2R mouse melanoma cell clone. Treatment of M2R cells with PMA resulted in a significant loss of beta-MSH binding. The effect was both time- and concentration-dependent. The inhibition of beta-MSH binding resulted from a decrease (greater than 85%) in active membranal receptors available on the external cell surface and not from either enhanced internalization or change in the binding affinity. Agonist-stimulated cyclic AMP accumulation was profoundly increased in a non-selective manner following short-term incubation (3 h) with PMA. This effect was completely reversed during long-term (72-96 h) incubation with the tumor promoting agent. Long-term culturing of M2R cells with PMA resulted in enhanced (+50%) proliferation of the melanoma cells. This enhancement was blocked by the addition of agents which stimulate the production of cAMP. Hence, phorbol esters are powerful growth promoters in transformed melanocytes and our findings indicate that the effects of melanotropins are selectively impaired during the process of growth promotion.
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PMID:Phorbol ester impairs melanotropin receptor function and stimulates growth of cultured M2R melanoma cells. 254 Sep 97

Murine adrenal tumor cells (Y-1 clone) were stimulated by adrenocorticotropic hormone (ACTH) and cyclic adenosine 3',5'-monophosphate (cyclic AMP) to produce steroid hormone (delta 4, 3-keto steroids). The steroids were secreted into the medium immediately after synthesis. The optimum concentrations of ACTH and cyclic AMP for stimulation of steroid production were 10(-2) U/ml and 1.0 mM, respectively. In serum-free medium, ACTH and cyclic AMP stimulated steroidogenesis in Y-1 cells, but the amount of steroid hormone in the culture medium was low. However, a high level of steroid production was maintained with medium containing 10 mg/ml bovine serum albumin (BSA). In culture medium containing a higher concentration of BSA, Y-1 cells did not become spherical as is usually the case when steroid production is stimulated by ACTH or cyclic AMP. The morphological changes did not always correlate with steroid secretion by Y-1 cells.
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PMID:Composition of culture media for steroid hormone secretion by murine adrenal tumor cells, Y-1 clone. 254 84

A yin-yang hypothesis is presented linking noradrenergic activity, thromboxane, melatonin, left hemisphere functioning, and cyclic AMP on the one hand, and dopamine, beta-endorphin, calcium, right hemisphere functioning, and cyclic GMP on the other. It is further suggested that there is a yoking of NA, TXA2, serotonin and melatonin in the left hemisphere, and a similar yoking of DA, BE, calcium and cGMP in the right. Evidence is presented to support the hypothesis that each element (NA, TXA2, etc.) on one side can modulate or balance a corresponding element (DA, BE, etc.) on the other. It is suggested that thromboxane is the key element in noradrenergic overactivity and that not taking this into consideration has confounded much prior research. This theory takes into account information processing models as well as pharmacological data and neurochemical theory on coupling of adenylate cyclase to its hormone receptors. Inhibiting noradrenergic overactivity can be obtained by inhibiting thromboxane and concomitantly activating opiate receptors. This protocol may have clinical utility in treating a wide range of disorders such as: anxiety, depression, schizophrenia, sleeplessness, withdrawal states, enuresis, Gilles de la Tourette syndrome, Parkinsonism, Alzheimers, dementia, anorexia, infant ruminations, essential tremor, spasticity of spinal cord injury, diarrhoea, ulcerative colitis, extrapyramidal symptoms, akathisia, neuroleptic malignant syndrome, attention deficit disorder, hyperhidrosis, and possibly AIDS.
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PMID:Inhibiting noradrenergic overactivity by inhibition of thromboxane and concomitant activation of opiate receptors via dietary means. 254 22

In adrenal glomerulosa cells, angiotensin II (AII) rapidly stimulates the formation of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and causes marked long-term changes in the levels of highly phosphorylated inositols. Glomerulosa cells prelabeled with [3H]inositol for 48 h and exposed to AII for 10 min showed prominent increases in inositol 1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P4) and smaller increases in two additional tetrakisphosphates, Ins-1,3,4,6-P4 and another (Ins-3,4,5,6-P4) eluting in the position of Ins-3,4,5,6-P4 and its stereoisomer, Ins-1,4,5,6-P4, on anion exchange liquid chromatography. A concomitant decrease in InsP5 indicates that an increase in Ins-1,4,5,6-P4, the breakdown product of InsP5, is probably responsible for the initial rise in Ins-3,4,5,6-P4 during 10 min stimulation by AII. During prolonged stimulation by AII, Ins-1,3,4,5-P4 began to decline from its high, stimulated level after the first hour but the level of Ins-1,3,4,6-P4 remained elevated for several hours. There were also progressive increases in the levels of Ins-3,4,5,6-P4 and InsP5 during stimulation for up to 16 h with AII. Treatment of adrenal cells for 16 h with the cyclic AMP-mediated secretagogue, adrenocorticotropic hormone (ACTH), slightly increased basal levels of Ins-1,3,4,6-P4, Ins-3,4,5,6-P4, and InsP5, and enhanced the subsequent AII-stimulated increases in the two additional tetrakisphosphate isomers but not of inositol trisphosphates or Ins-1,3,4,5-P4. This change in the pattern of the higher inositol phosphate response to AII was manifested within 2 h after exposure to ACTH, and was mimicked by treatment with 8-bromo cyclic AMP or forskolin. Treatment with 50 microM cycloheximide abolished the ACTH-induced increases in inositol polyphosphate responses during AII stimulation, but had no effect on the responses of untreated cells to AII. The conversion of [3H]Ins-1,3,4-P3 to [3H]Ins-1,3,4,6-P4, a reaction linking the receptor-mediated InsP3 response to higher inositol phosphates, was enhanced in permeabilized cells that were pretreated for 16 h with either ACTH or AII. These results demonstrate that the reactions by which Ins-1,3,4,6-P4 and Ins-3,4,5,6-P4 are formed and converted to InsP5 are influenced by agonist-stimulated regulatory processes that include both calcium-dependent and cyclic AMP-dependent mechanisms of target cell activation. They also reveal changes consistent with agonist-induced conversion of InsP5 to its dephosphorylated metabolite, Ins-1,4,5,6-P4, during short-term stimulation by AII.
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PMID:Agonist-induced regulation of inositol tetrakisphosphate isomers and inositol pentakisphosphate in adrenal glomerulosa cells. 254 68

The possible role of protein kinase C (PKC) in the cyclic AMP-dependent mechanism of action of corticotropin-releasing factor (CRF) on proopiomelanocortin cells of anterior and intermediate pituitary glands was examined after pretreatment of cells in culture with the PKC inhibitor retinal or the phorbol ester PMA, which depletes cell stores of the kinase. We found that these drugs not only abolished ACTH response to PMA and vasopressin, which both activate PKC, but unexpectably also dampened by 80-90% the stimulatory effect of CRF. Cell treatment with retinal failed to prevent CRF-induced accumulation of cyclic AMP. Retinal and PMA pretreatments of intermediate pituitary cells likewise inhibited alpha-MSH secretion stimulated by CRF. These data provide evidence to suggest that the mechanism of action of CRF on pituitary cells involves both cyclic AMP and PKC messenger systems.
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PMID:Indirect evidence that protein kinase C plays a critical role in signal transduction of both vasopressin and corticotropin-releasing factor on pituitary cells in culture. 255 Dec 65

Transforming growth factor beta (TGF beta) is a potent inhibitor of adrenocortical cell differentiated functions, whereas corticotropin (ACTH) is the main physiological hormone which acts positively on these functions. We have studied the effects of both TGF beta and ACTH on ovine adrenocortical cell ACTH receptors. Ovine adrenocortical cells contained specific high affinity (Kd = 2.7 +/- 1.6 x 10(-10) M) and low capacity (1190 +/- 120 sites/cell) ACTH receptors. Pretreatment of cells with TGF beta resulted in a time- and dose-dependent (ED50 = 50 pg/ml) decrease of 125I-ACTH1-39 binding. The observed decrease in ACTH binding was due to a 2-3-fold decrease in the number of binding sites without modification of the binding affinity. On the contrary, pretreatment of cells with ACTH caused a 4-4.5-fold increase in the number of ACTH binding sites without an effect on the Kd. When cells were pretreated with both ACTH and TGF beta, TGF beta blocked completely the positive trophic effect of ACTH on its own receptors. The variations in ACTH receptor number were associated with parallel changes on acute ACTH-induced cyclic AMP production. Thus, the effects of TGF beta on ACTH receptor content are likely another important negative action of this peptide on adrenocortical cell differentiation. Moreover, these results suggest that regulation of ACTH receptor number may be one mechanism by which hormones and growth factors control adrenocortical differentiation.
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PMID:Transforming growth factor beta treatment decreases ACTH receptors on ovine adrenocortical cells. 255 31

In Bomirski Ab amelanotic hamster melanoma cells, L-tyrosine and/or L-dopa induce increases in tyrosinase activity as well as synthesis of melanosomes and melanin. L-tyrosine also modifies melanocyte-stimulating hormone (MSH) binding. In this paper we show that in the Bomirski amelanotic melanoma system MSH and agents that raise intracellular cyclic AMP induce dendrite formation, inhibit cell growth, and cause substantial increases in tyrosinase activity without inducing melanin synthesis. Tyrosinase activity is detected only in broken cell preparations, or cytochemically in fixed cells. In the continued absence of mature melanosomes, the induced enzyme remains in elements of the trans-Golgi reticulum. Comparative measurements of cyclic AMP in amelanotic and tyrosine-induced melanotic cells show similar basal levels. L-tyrosine and L-dopa have little or no effect, whereas MSH may cause a 1000% peak increase in cyclic AMP levels both in amelanotic and melanotic cells. None of these agents influences cyclic GMP or inositol trisphosphate (InsP3) levels. In agreement with the InsP3 assays, phorbol ester (TPA) has no effect on melanization, tyrosinase activity or cell proliferation. In conclusion, in the Bomirski amelanotic melanoma, MSH induces only partial cell differentiation associated with raised levels of cyclic AMP. Induction of melanosome synthesis and melanization by L-tyrosine or L-dopa appear to follow pathways unrelated to cyclic AMP, cyclic GMP or InsP3.
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PMID:MSH inhibits growth in a line of amelanotic hamster melanoma cells and induces increases in cyclic AMP levels and tyrosinase activity without inducing melanogenesis. 255 57

To assess the effects of corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH) on airway ciliary activity, we measured ciliary beat frequency (CBF) by a photoelectric method in response to these peptides in cultured rabbit tracheal explants. When cumulatively added, both CRF and ACTH increased CBF in a dose-dependent fashion. Treatment of tissues with Ca2+-free medium or nifedipine abolished the effect of CRF but not of ACTH. The CRF- and ACTH-induced ciliostimulations were not affected by indomethacin or autonomic antagonists, but were attenuated by nordihydroguaiaretic acid and by their receptor antagonists, alpha-helical CRF (9-41) and ACTH (7-38). Intracellular cyclic AMP levels were significantly increased by CRF and ACTH. These results suggest that CRF and ACTH stimulate airway ciliary motility through the activation of adenylate cyclase and lipoxygenase by binding to their specific receptors, where the effect of CRF may be triggered by Ca2+ influx.
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PMID:Corticotropin-releasing factor and adrenocorticotropin stimulate ciliary motility in rabbit tracheal epithelium. 255 12

Corticotropin releasing hormone (CRH) stimulation of ACTH release and cyclic AMP-mediated events involved in the control of ACTH release were compared in sham-operated and adrenalectomized rats. CRH-stimulated adenylate cyclase activity was decreased in pituitary homogenates from adrenalectomized animals. CRH-stimulated cyclic AMP accumulation was essentially abolished and CRH-stimulated cyclic AMP-dependent protein kinase (A-kinase) activity was decreased in freshly prepared anterior pituitary cells from adrenalectomized animals. Basal and CRH-stimulated ACTH release was elevated in these cells. Since ACTH release is increased in adrenalectomized rats despite the down regulation of CRH-linked pituitary mechanisms, we speculate that the site of action of disinhibition by corticosterone of ACTH release (or synthesis) following adrenalectomy is distal to the generation of cyclic AMP and/or that non-CRH mediated mechanisms assume a greater role in ACTH regulation following adrenalectomy.
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PMID:Effects of adrenalectomy on CRH regulation of ACTH release: adenylate cyclase activity, cyclic AMP-dependent protein kinase activity and ACTH release. 256 46

Cachectin (tumor necrosis factor) is a powerful macrophage hormone released during infection, which circulates in blood to produce diverse effects in the organism. We examined the effect of cachectin on release of anterior pituitary hormones from either hemipituitaries or dispersed pituitary cells incubated in vitro. The action of cachectin on dispersed cells was demonstrable only after 2 hr of incubation. With this incubation time, the protein produced a dose-related stimulation of release of adrenocorticotropin (ACTH), growth hormone (GH), and thyrotropin (TSH), but not of prolactin (Prl), from both hemipituitaries and dispersed cells. The doses required for stimulation were low in the case of hemipituitaries, usually of the order of 10(-12) M, whereas they were higher by one or two orders of magnitude with the dispersed pituitary cells. This may be related either to loss of receptors for the protein during the dispersion procedure or to the fact that in the hemipituitary system cell interactions are facilitated because the cells are close to each other. In the dispersed cell system cachectin evoked a dose-related decrease in cyclic AMP content. Incubation with somatostatin lowered the cyclic AMP content of the cells and depressed GH output without altering output of TSH or Prl. When somatostatin and cachectin were incubated together with the cells, the suppression of cyclic AMP production was abolished; TSH and Prl release were stimulated, but the action of cachectin to stimulate GH release was blocked. The stimulation of Prl release by cachectin in the presence of somatostatin may be related to the elevation of cyclic AMP, a known stimulator of Prl release. The cyclooxygenase inhibitor indomethacin nearly completely blocked the stimulatory effect of cachectin on release of GH and TSH from dispersed pituitary cells but had only a slight and nonsignificant attenuating effect on its ACTH-releasing action. These results suggest that at least part of the stimulatory action of the peptide on pituitary hormone release is brought about by prostaglandins. The failure of indomethacin to block the release of ACTH induced by cachectin suggests that other mechanisms may be involved in the release of ACTH induced by this peptide. Since the concentrations of cachectin required to stimulate pituitary hormone release are similar to those that are encountered in plasma during infection, it is likely that this direct pituitary action has pathophysiological significance.
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PMID:Cachectin alters anterior pituitary hormone release by a direct action in vitro. 256 80


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