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)

beta-Endorphin 1-31 and several structurally related peptides were tested for their ability to alter mitogen-induced T cell proliferation. Rat beta-endorphin 1-31 and human beta-endorphin 1-27 increased phytohemagglutinin (PHA)-induced [3H]thymidine incorporation into rat lymph node cells. However, when PHA-induced proliferation was suppressed by the inclusion of prostaglandin E1 (PGE1), human beta-endorphin 1-31 and a number of structurally similar peptides, including some peptides that did not alter mitogen-induced proliferation, significantly reduced the PGE1 inhibition of PHA-stimulated T cell proliferation. Although the N-terminus of beta-endorphin was necessary for potency, inclusion of the opioid antagonist naloxone together with beta-endorphin 1-31 did not alter the blockage of PGE1 inhibition of PHA-induced proliferation caused by beta-endorphin. The inhibition of mitogen-stimulated proliferation by either cholera toxin or forskolin, two additional compounds that like PGE1 also elevate cyclic AMP levels, was not blocked by beta-endorphin. Verapamil suppression of proliferation was not modified by beta-endorphin, indicating that the beta-endorphin stimulatory effect was probably not due to Ca2+ influx through verapamil-sensitive Ca2+ channels. These data suggest that beta-endorphin, acting through a nonopioid beta-endorphin receptor, may modulate immunocompetence by stimulating T cell proliferation and by counteracting the inhibitory effects of PGE1.
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PMID:Beta-endorphin stimulates rat T lymphocyte proliferation. 217 Apr 40

Tyrosinase synthesis and its regulation in human melanocytes was studied by measuring the incorporation of [35S] methionine into incubated skin biopsies. Tyrosinase was detected in all skin samples with the highest levels in skin type IV and the lowest levels in skin type I. Following psoralen ultraviolet A (PUVA) therapy for several weeks, significant increases in the amounts of tyrosinase were found in skin types III and IV. The presence of alpha-melanocyte-stimulating hormone (alpha-MSH) (100 mumol/l) or the long-acting analogue [Nle4, DPhe7] alpha-MSH (1-10 mumol/l) in the incubation medium failed to alter tyrosinase levels in the skin biopsies taken from patients both before and after receiving PUVA therapy. Bromo-adenosine 3,5-cyclic monophosphate sodium salt (8-bromo-cAMP) (10 mmol/l), on the other hand, increased the amounts of tyrosinase both before and after PUVA, but these effects were only seen in biopsies of type III and IV skin. These results indicate that MSH fails to stimulate tyrosinase synthesis in human melanocytes. Nevertheless, tyrosinase synthesis and its regulation by cyclic AMP-dependent mechanisms could be important control points in the pigmentary response.
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PMID:Tyrosinase synthesis in different skin types and the effects of alpha-melanocyte-stimulating hormone and cyclic AMP. 217 91

To elucidate the role of the diacylglycerol-protein kinase C (PKC) pathway in beta-endorphin synthesis and secretion in anterior pituitary corticotrope tumor cells (AtT-20), a procedure for down-regulating PKC activity in the cells was developed. Treatment of AtT-20 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) led to an increase in [3H]phorbol 12,13-dibutyrate binding to PKC in the membrane fraction of these cells 30 s after its addition to the culture medium. Thereafter, a decrease in both [3H]phorbol 12,13-dibutyrate binding and PKC-specific phosphotransferase activity occurred in a time- and dose-dependent manner in both the cytosolic and membrane fractions. For example, treatment of the cells with 100 nM TPA for 24 h resulted in an almost complete depletion of PKC activity. Immunoreactive beta-endorphin secretion was found to be stimulated two- to fourfold in the control cells after incubation with corticotropin-releasing factor (10(-7) M), forskolin (10(-6) M), or TPA (10(-7) M) for 4 h. In cells rendered PKC deficient, TPA-stimulated immunoreactive beta-endorphin release was abolished, forskolin-stimulated release was unaffected, and corticotropin-releasing factor-stimulated release was depressed. Treatment of control cells with any one of the three stimulatory agents led to an increase in proopiomelanocortin mRNA levels, and these responses were also depressed after TPA pretreatment. The results suggest that physiological processes thought to be entirely cyclic AMP dependent, such as corticotropin-releasing factor-elicited secretion, may be partially dependent on PKC-mediated biochemical events.
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PMID:Effects of protein kinase C down-regulation on secretory events and proopiomelanocortin gene expression in anterior pituitary tumor (AtT-20) cells. 229 16

Somatostatin and carbachol receptors are believed to be negatively coupled to adenylate cyclase in AtT-20 mouse pituitary tumor cells by an inhibitory guanine nucleotide-binding regulatory subunit. Activation of these receptors causes inhibition of cyclic AMP synthesis and adrenocorticotropin (ACTH) secretion stimulated by a variety of hormones. Secretion in response to several pharmacological agents, which do not increase AtT-20 cyclic AMP levels, is also antagonized by both somatostatin and carbachol. Inasmuch as ACTH secretion in response to all stimulants is dependent on extracellular calcium, the possibility that somatostatin and carbachol block calcium entry was investigated by observing the effects of these agents on the activity of the calcium channel activator, BAY-K-8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4- (2-trifluoromethylphenyl)-pyridine-5-carboxy-late] in AtT-20 cells. In first characterizing the effect of BAY-K-8644, it was noted that the channel agonist at 10(-10) to 10(-6) M itself rapidly increased basal ACTH secretion; higher concentrations (10(-4) M) reduced basal, (-)-isoproterenol, phorbol ester, 8-Br-cAMP and K+-stimulated secretion. BAY-K-8644 did not alter basal formation of cyclic AMP. The secretory response to BAY-K-8644 was dependent on extracellular calcium, and was inhibited by the calcium channel antagonist, nifedepine. When coapplied with (-)-isoproterenol, phorbol ester and 8-Br-cAMP, at a concentration which optimally stimulated ACTH secretion, BAY-K-8644 had an additive effect; the secretory responses to K+ (50 mM) or the calcium ionophore, A-23187, on the other hand, were potentiated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of adrenocorticotropin secretion from AtT-20 cells by the calcium channel activator, BAY-K-8644, and its inhibition by somatostatin and carbachol. 241 8

The demonstrations that Ro 5-4864, a ligand selective for the peripheral-type benzodiazepine (BZD) binding site, inhibited cellular differentiation and proliferation and that occupancy of the peripheral-type BZD binding site likely mediated the observed BZD effects on diverse endocrine tissues suggested that Ro 5-4864 disrupted a common cellular regulatory event. Using a well-characterized anterior pituitary-derived tumor cell line (AtT-20 cells), which synthesizes and secretes adrenocorticotropic hormone (ACTH), beta-lipotropin hormone (beta-LPH), and beta-endorphin (BE), we have investigated the molecular mechanism of action of Ro 5-4864's capacity to alter BE secretion. Ro 5-4864 inhibits basal and induced BE release from AtT-20 cells, through a cyclic AMP-independent mechanism. Ro 5-4864 completely blocked the corticotropin-releasing hormone and forskolin-induced release of BE without altering the concomitant production of cyclic AMP. The addition to AtT-20 cells of CGP 28392, a dihydropyridine that has been demonstrated in other systems to specifically activate voltage-dependent Ca2+ channels, resulted in a cyclic AMP-independent, dose-related increase in BE secretion. This CGP-induced BE release was blocked by increasing concentrations of Ro 5-4864. In contrast to the capacity of Ro 5-4864 to block CGP-induced BE release, Ro 5-4864 lacked the capacity to block enhanced BE secretion due to the calcium ionophore A23187, which increases intracellular Ca2+ levels independent of the voltage-dependent Ca2+ channels. Our findings suggest that Ro 5-4864 inhibits BE secretion from AtT-20 cells through a blockade of the voltage-dependent membrane Ca2+ channels and this mechanism of action may be responsible for Ro 5-4864's diverse effects observed on other cell types.
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PMID:Evidence that the peripheral-type benzodiazepine receptor ligand Ro 5-4864 inhibits beta-endorphin release from AtT-20 cells by blockade of voltage-dependent calcium channels. 242 32

Intracellular recordings from primary mechanosensory neurones (dorsal cells) in the lamprey spinal cord were used to test the membrane effects of a variety of putative neuromodulatory agents. gamma-Aminobutyric acid (GABA) produced a dose-dependent increase in the duration of mixed Na-Ca or pure Ca action potentials in these cells. L-Glutamate and glycine produced minimal broadening of Ca action potentials. Acetylcholine, noradrenaline, serotonin, met-enkephalin, D-glutamate and dopamine had no effect. The pharmacology of GABA's action appeared to be complex. While the GABAA receptor antagonists, bicuculline, picrotoxin and curare, did not block GABA's effect, both the GABAA receptor agonist, muscimol, and the GABAB-receptor agonist, baclofen, occasionally broadened Ca action potentials in these cells. GABA had no effect on the resting potential, passive current-voltage (I-V) characteristics and pure Na action potential of dorsal cells, ruling out an action on passive membrane channels, transmitter-activated channels, or on those voltage-dependent channels activated during the Na action potential. Thus, GABA affected dorsal cells only when a significant Ca current was evident. GABA appeared not to increase the conductance of the Ca channels since its action was accompanied by an increase in input resistance, suggesting an inhibition of Ca-dependent conductance that normally acts to repolarize the membrane during a Ca action potential. An inhibitory effect of GABA on a Ca-dependent Cl conductance was ruled out in experiments where the Cl gradient was altered by removal of extracellular Cl without affecting GABA-induced Ca action potential prolongation. Dorsal cells have a prominent Ca-dependent K conductance (gK(Ca], and it is this conductance that GABA may inhibit. Consistent with this was the observation that the hyperpolarizing after-potential that follows Ca action potentials in dorsal cells, which reflects gK(Ca) in these cells and whose duration is normally increased when the Ca action potential duration increases, was not prolonged when the Ca action potential was broadened by GABA. Further, the failure of GABA to prolong Ba action potentials was consistent with this proposed mechanism of action, since Ba apparently does not activate gK(Ca) in these cells. Forskolin, a specific adenylate cyclase activator, caused broadening of Ca action potentials in lamprey dorsal cells comparable in magnitude to that of GABA. Thus, an increase in intracellular cyclic AMP is a candidate for the intracellular mediator of GABA's effect on these cells.
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PMID:Prolongation of calcium action potentials by gamma-aminobutyric acid in primary sensory neurones of lamprey. 243 26

1. Macroscopic and single-channel currents were recorded from voltage-clamped neurones in the abdominal and pleural ganglia of Aplysia californica in order to investigate conductance changes elicited by application of the endogenous peptide FMRFamide (Phe-Met-Arg-Phe-NH2) and related neuropeptides to the cell surface. 2. The Ca-dependent K current, IK(Ca), when elicited at a constant voltage by intracellular injection of Ca2+, was insensitive to FMRFamide or its derivative YGG-FMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2). 3. Under steady voltage clamp, certain cells responded to a brief puff of FMRFamide or YGG-FMRFamide with a transient outward current lasting about 1 min. Unclamped cells responded with a corresponding hyperpolarization. These responses reversed at about -75 mV. Ion substitution indicated that the current is carried by K+. 4. FMRFamide and YGG-FMRFamide were equally effective in activating the outward current, whereas FMRF, met-enkephalin and leu-enkephalin were ineffective. 5. At voltages negative to -30 mV and, in the absence of extracellular Ca2+, also at more positive potentials, the FMRFamide-sensitive current showed no voltage dependence beyond that predicted from constant-field considerations. 6. The response to FMRFamide was relatively insensitive to extracellular tetraethylammonium (TEA, KD approximately 75 mM) and 4-aminopyridine (4-AP, KD approximately 6 mM). It was suppressed in Ba-containing solutions, but was unaffected by injection of the Ca chelating agent EGTA. The response was blocked by serotonin and other agents known to elevate intracellular adenosine 3',5'-phosphate (cyclic AMP) levels, and by direct injection of cyclic AMP into the cell. 7. In its pharmacological properties and lack of voltage dependence, the FMRFamide-activated current resembles the 'S' current, IK(S), a K current suppressed by application of serotonin in Aplysia neurones. 8. The similarity between the FMRFamide-sensitive current and the 'S' current was confirmed in cell-attached patch-clamp studies, in which activity of 'S' channels was found to be reduced by serotonin, and enhanced by FMRFamide. 9. Thus, FMRFamide may function in Aplysia to counteract the serotonergic modulation of 'S' channels, which has been proposed as a mechanism of presynaptic plasticity in this mollusc.
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PMID:Modulation of potassium conductances by an endogenous neuropeptide in neurones of Aplysia californica. 244 63

The paper is concerned with a study of the mechanism of ethanol induced testosterone biosynthesis inhibition in rat testis. The time course of acute alcoholic intoxication (4 g of ethanol per 1 kg of body mass) has shown that the size and direction of testosterone concentration shifts resemble those of corticosterone. The level of the latter correlates with the ethanol concentration rising at the early time of the experiment and lowering up to 26-27% in 4-8 h. The content of testis cyclic AMP, leu-enkephalin and beta-endorphin remains unchanged indicating against the hypothesis of ethanol effects mediation by the testicular opioid system.
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PMID:[Mechanism of suppression of testosterone biosynthesis by ethanol]. 252 63

Forskolin, an activator of adenylate cyclase, stimulates adrenocorticotropin (ACTH) release and increases proopiomelanocortin mRNA levels in anterior pituitary cells by enhancing cyclic AMP (cAMP)-dependent protein kinase activity. The phorbol ester phorbol 12-myristate 13-acetate (PMA) evokes these same responses from anterior pituitary cells by activating protein kinase C. Both protein kinases most likely induce their cellular effects by catalyzing the phosphorylation of specific proteins. To elucidate the mechanisms by which cAMP-dependent protein kinase and protein kinase C promote ACTH secretion and synthesis, the phosphoproteins regulated by forskolin and PMA were identified in the cell line AtT-20, which consists of a homogeneous population of corticotrophs. Phosphoproteins were analyzed in different subcellular fractions by two-dimensional polyacrylamide gel electrophoresis and autoradiography. Forskolin increased phosphate incorporation into two proteins in the cytoplasmic fraction of 24 kilodaltons (kd) (pI 6.8) and 40 kd (pI 5.8), two proteins in the plasma membrane fraction of 32 kd (pI 8.3) and 60 kd (pI 8), and one protein in the nuclear fraction of 20 kd (pI 8.7). Insertion of the inhibitor of cAMP-dependent protein kinase into the AtT-20 cells, using a liposome technique, blocked the rise in phosphate incorporation induced by forskolin. PMA also stimulated phosphate incorporation into proteins in AtT-20 cells. PMA increased the phosphorylation of three cytoplasmic proteins of 25 kd (pI 7.6), 40 kd (pI 5.8), and 40 kd (pI 8.1) as well as two membrane proteins of 32 kd (pI 8.3) and 60 kd (pI 8) and one nuclear protein of 20 kd (pI 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein phosphorylation induced by phorbol esters and cyclic AMP in anterior pituitary cells: possible role in adrenocorticotropin release and synthesis. 253 66

Coordinate secretion of two prohormone/proneuropeptide processing enzymes [pro-opiomelanocortin converting enzyme (PCE) and an aminopeptidase B-like enzyme (APBE)] and alpha-melanotropin (alpha-MSH) from bovine intermediate lobe pituitary cells was studied. Stimulation of secretion with 8-bromo-cyclic AMP produced significant increases in levels of immunoreactive alpha-MSH, PCE, and APBE. Treatment of cells with the dopaminergic agonist 2-bromo-alpha-ergocryptine resulted in significant decreases in secretion of alpha-MSH, PCE, and APBE. In neither case were there significant changes in levels of cytosolic lactic dehydrogenase or lysosomal beta-glucuronidase in the medium. The secreted PCE activity was shown to process frog and mouse pro-opiomelanocortin primarily to 23,000-Mr corticotropin (ACTH), 13,000-Mr ACTH, beta-lipotropin, a beta-endorphin-like peptide, and beta-endorphin, products comparable to those synthesized by the mouse and frog intermediate lobe in situ. The secreted enzymatic activity had a pH optimum between 4.0 and 5.0, was strongly inhibited by pepstatin A, and had an inhibitor profile similar to the purified bovine intermediate lobe PCE. The secreted APBE activity cleaved Argo-[Met]-enkephalin to [Met]-enkephalin and had a pH optimum and inhibitor profile similar to that previously reported for an activity from purified secretory vesicle fractions of bovine intermediate and neural lobes. The coordinate regulated secretion of alpha-MSH and enzyme activities (PCE and APBE) strongly indicates their colocalization in the same secretory vesicle compartment within the cell. The characteristics of the two enzymes secreted in the medium paralleled those seen in the tissue and further support their role in pro-opiomelanocortin processing in vivo.
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PMID:Regulated secretion of pro-opiomelanocortin converting enzyme and an aminopeptidase B-like enzyme from dispersed bovine intermediate lobe pituitary cells. 254 Feb 80


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