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)

Heavy metals including mercury, cadmium, cobalt, and copper (100 microM) exerted an adverse effect on the viability of isolated rat adrenal capsular (zona glomerulosa), adrenal decapsular (fasciculata and reticularis), and Leydig cells of the testis, with mercury being the most potent. Due to the decreased cell viability there was a parallel reduction in corticotropin-stimulated corticosterone production by adrenal decapsular cells and luteinizing hormone-stimulated testosterone production by Leydig cells. The results indicated a direct toxic action of these heavy metals on steroid-producing cells in the adrenal gland and the testis. Other metals tested, including lead, zinc, aluminum, chromium, iron, nickel, and lithium, did not exert any deleterious effect on cell viability or hormone-induced steroidogenesis in adrenal and Leydig cells when tested up to a concentration of 100 microM.
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PMID:Toxic effect of heavy metals on cells isolated from the rat adrenal and testis. 215 92

Synthetic corticotropin-releasing factor (CRF) is a potent adrenocorticotropin (ACTH) secretagogue in the mouse pituitary tumor cell strain AtT20/D16v (D16). In the absence of added calcium in the incubation medium a dose of 5 nM CRF stimulates ACTH secretion 2-fold over control values while at medium calcium concentrations greater than 1 mM the same dose of CRF elicits a 3-fold stimulation. In the presence of EGTA or of the calcium antagonists verapamil, cobalt, or lanthanum the CRF effect is abolished. Depolarizing concentrations of extracellular K+ lead to a rapid increase in cell-associated calcium, a response which is inhibited by the dihydropyridine calcium antagonist nimodipine. Although treatment with CRF does not alter the concentration of cell-associated calcium in D16 cells, ACTH secretion stimulated by both CRF and elevated medium K+ are inhibited by nimodipine in a dose-related manner. The results indicate that D16 cells possess both voltage-sensitive and CRF-activated calcium channels.
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PMID:Multiple classes of calcium channels in mouse pituitary tumor cells. 241 85

The role of extracellular Ca2+ in pituitary hormone release was studied in primary cultures of rat anterior pituitary cells. The basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH), and adrenocorticotropin (ACTH) secretion were independent of extracellular Ca2+ concentration ([Ca2+]e). In contrast, the basal levels of growth hormone (GH) and prolactin (PRL) release showed dose-dependent increases with elevation of [Ca2+]e, and were abolished by Ca2+-channel antagonists. Under Ca2+-deficient conditions, BaCl2 mimicked the effects of calcium on PRL and GH release but with a marked increase in potency, and also increased basal LH and FSH release in a dose-dependent manner. In the presence of normal [Ca2+]e, depolarization with K+ maximally increased cytosolic [Ca2+] ([Ca2+]i) from 100 to 185 nM and elevated LH, FSH, TSH, ACTH, PRL, and GH release by 7-, 5-, 4-, 3-, 2-, and 1.5-fold, respectively. These effects of KCl were abolished in Ca2+-deficient medium or in the presence of the Ca2+-channel antagonist, Co2+, and were diminished by the dihydropyridine Ca2+-channel antagonist, nifedipine. The Ca2+-channel agonist BK 8644 (100 nM) enhanced the hormone-releasing actions of 25 mM KCl upon PRL, LH, FSH, GH, TSH, and ACTH by 2.3-, 2.0-, 1.8-, 1.7-, 1.6-, and 1.4-fold, respectively. The dose- and voltage-dependent actions of BK 8644 were specific for individual cell types; BK 8644 enhanced GH, PRL, TSH, LH, and ACTH secretion in the absence of any depolarizing stimulus, with ED50 values of 8, 10, 150, 200, and 400 nM, respectively. However, in the presence of 50 mM KCl, the ED50 values for BK 8644 were 1.5, 2, 3, 5, and 7 nM for GH, PRL, ACTH, TSH, and LH, respectively. [3H]BK 8644 bound specifically to pituitary membranes with Kd values of 0.8 nM and concentrations of about 900 channels per cell. These observations provide evidence for the presence and participation of voltage-sensitive calcium channels in the secretion of all five populations of anterior pituitary cells.
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PMID:Participation of voltage-sensitive calcium channels in pituitary hormone release. 245 42

Of three casein phosphatases isolated from the cytosol of human cord blood erythrocytes two were cobalt-dependent, E2 and E3. In the presence of CoCl2, E2 activity was the most prominent. In addition to casein, E2 dephosphorylated phosvitin and p-nitrophenyl phosphate (p-NPP) with pH optima at 6.8-7.2 for proteins and 9.0 for p-NPP. The native enzyme had a molecular weight of 104,000 daltons after AcA-44 Ultrogel filtration. According to SDS/PAGE it consisted of two subunits, 78,000 and 15,000 daltons. The 104,000-dalton form exhibited Michaelis-Menten kinetics and had the greatest affinity for casein between protein substrates tested. Ethanol denaturated the enzyme by 80%. Optimal activation of E2 phosphatase was achieved with 5 mmol/l CoCl2 which did not affect the catalytic properties of the enzyme but did affect the rate of 'E-S' complex formation. Inorganic pyrophosphate was not inhibitory for the 104,000-dalton enzyme. Judging by all these properties the natural substrate for E2 casein phosphatase could be P-pyruvate kinase.
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PMID:Cobalt-dependent protein phosphatases from human cord blood erythrocytes. II. Further characterization of E2 casein phosphatase. 283 85

Peptide hormones are synthesized from larger precursors by cleavages at paired basic residues. We have isolated a pro-hormone converting enzyme from bovine neural and intermediate lobe secretory vesicles that cleaves pro-vasopressin and pro-opiomelanocortin at Lys-Arg residues to yield vasopressin, and adrenocorticotropin/endorphin-related peptides, respectively. The enzyme from both lobes is an aspartyl protease of approximately 70,000 Da, is a glycoprotein and has an optimum pH range of 4.0-5.0. Present within the same secretory vesicles is an aminopeptidase B-like enzyme which is a metalloprotease that is inhibited by Co2+ and Zn2+. This enzyme may play a role in trimming off the N-terminal extended basic residues from peptides liberated by the pro-hormone converting enzyme.
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PMID:Pro-opiomelanocortin and pro-vasopressin converting enzyme in pituitary secretory vesicles. 284 Sep 73

The ionic conductance mechanisms underlying the action potential behaviour of frog melanotrophs in primary culture were studied by using the patch-clamp technique in whole-cell configuration. The action potentials spontaneously generated by these cells were predominantly sodium spikes with a calcium component. Voltage-dependent sodium, calcium, potassium and calcium-activated potassium currents were identified and analysed separately. The voltage-dependent sodium current was characterized by its fast kinetic, its low-threshold activation, its voltage-dependent inactivation and a tetrodotoxin sensitivity. Calcium currents were identified on the basis of their ionic selectivity to divalent cations (Ba2+, Ca2+, Co2+) and their time course. Only two of the three well-documented calcium currents could be detected in frog melanotrophs. A sustained calcium current (ICaS) and an inactivating calcium current (ICaN) were elicited by step depolarizations up to -20 mV. ICaN inactivated for membrane potentials more positive than -50 mV; its inactivation appeared to be both voltage- and calcium-dependent. Transient calcium current (ICaT) has never been observed. Two types of potassium currents were identified: voltage-dependent potassium (IKV) and calcium-activated potassium currents, (IK[Ca]). They were both suppressed by tetraethylammonium chloride, whereas only IK(Ca) was blocked by cobalt. These major ionic currents underlying spontaneous electrical activity are assumed to be involved in the process of alpha-melanocyte-stimulating hormone release. The present study provides the ground for future investigations regarding the relationships between the electrical and secretory activities in amphibian pars intermedia cells.
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PMID:Patch-clamp study of the ionic currents underlying action potentials in cultured frog pituitary melanotrophs. 285 22

The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.
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PMID:Endocrine function following high dose proton therapy for tumors of the upper clivus. 313 12

The effect of modifications of extracellular calcium concentrations on alpha-MSH release has been studied using perifused frog neurointermediate lobes. Increasing concentrations of calcium (from 2 to 10 mmol/l) gave rise to a dose-related stimulation of alpha-MSH secretion, whereas reduction of Ca2+ from 2 to 1.5 mmol/l partially inhibited alpha-MSH release. The direct effect of extracellular Ca2+ on alpha-MSH secretion was confirmed by the dose-dependent stimulation of alpha-MSH release induced by the calcium ionophore A23187. Perifusion with a calcium-free medium or blockade of Ca2+ channels by 4 mmol Co2+/l both resulted in an inhibition of spontaneous and TRH-induced alpha-MSH release. Conversely, administration of verapamil or methoxyverapamil (10 mumol/l each) did not alter basal secretion and had no effect on the response of the glands to TRH. Nifedipine (10 mumol/l), which was able to block KCl (20 mmol/l)-evoked alpha-MSH release, induced a slight inhibition of basal alpha-MSH secretion, indicating that extracellular Ca2+ levels may regulate alpha-MSH release in part by Ca2+ influx through voltage-dependent Ca2+ channels. In contrast TRH-induced alpha-MSH release was not affected by nifedipine or dantrolene (10 mumol/l), and BAY-K-8644 (1 mumol/l) did not significantly modify the response of neurointermediate lobes to TRH. Taken together, these results suggest that TRH-induced alpha-MSH secretion is associated with calcium influx across the plasma membrane and that calcium entry caused by TRH may occur through nifedipine/verapamil-insensitive Ca2+ channels.
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PMID:Role of calcium in thyrotrophin-releasing hormone-stimulated release of melanocyte-stimulating hormone from frog neurointermediate lobe. 315 Dec 49

Corticotropin releasing factor (CRF)-containing afferents to the rat lateral septum (LS) have been determined by means of cobalt-enhanced immunohistochemistry, tracing of retrograde transport of horseradish peroxidase (HRP), and by lesioning experiments. When unilateral lesions included the rostral part of the hypothalamus, CRF-like immunoreactive (CRFI) ipsilateral fibers in the LS decreased in number. Lesions in other brain regions did not cause alterations in the septal CRFI fibers. These findings suggest that the septal CRFI fibers originate in the rostral part of the hypothalamus. Furthermore, combined HRP and immunohistochemical staining on the same sections demonstrated double-labeled cells in two discrete areas within the rostral hypothalamus: one was the perifornical hypothalamic area (PeF) at the level of the paraventricular hypothalamic nucleus, and the other was the most caudal part of the anterior hypothalamic nucleus (AHc). These findings show that a large proportion of the CRFI projections to the LS have their origins in the PeF and AHc.
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PMID:Corticotropin releasing factor-containing afferents to the lateral septum of the rat brain. 325 89

Some properties of inorganic pyrophosphatase (PPiase EC 3.6.1.1.) and para-nitrophenylphosphatase (p-NPPase EC 3.1.3.1) in the microsomal fraction of odontoblasts were investigated. The ratio of Mg2+:p-NPP and Mg2+:PPi for optimal enzyme activities was 1:1. A mutual substrate competition for PPiase and p-NPPase was described. In the presence of 0.1 mM EDTA, Mg2+ alone was not able to reactivate p-NPPase or PPiase. Instead, Zn2+ and Co2+ reactivated the PPiase, indicating they might act as cofactors for the enzyme. Mg2+ increased the PPiase activity, probably because Mg PP2-i was the true substrate for the enzyme. The diphosphonates ethane-1-hydroxy 1,1 diphosphonate (EHDP), methane diphosphonate (MDP) and dichloromethane diphosphonate (Cl2MDP) inhibited the PPiase activity.
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PMID:Relationship of inorganic pyrophosphatase and para-nitrophenylphosphatase activities of alkaline phosphatase in the microsomal fraction of isolated odontoblasts. 612 84


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