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)

In mineralizing dental tissues the non-specific alkaline phosphatase, using paranitrophenylphosphate (p-NPP) as substrate, is also capable of splitting inorganic pyrophosphate (PPi). In contrast to the p-NPP-ase part of the enzyme, the PPi-ase part requires Zn2+ as a cofactor for its hydrolytic activity. The PPi-ase activity of the enzyme can be inhibited by cadmium ions (Cd2+), perhaps by replacing Zn2+ from the active site of the enzyme molecule. In addition to splitting PPi, the PPi-ase part of the enzyme may also be involved in the phosphorylation process of yet undetermined organic macromolecules. Cd2+ inhibits this phosphorylation process. Inhibition of the PPi-ase activity can also be accomplished by ascorbic acid known for its capacity to complex bivalent cations. Ascorbic acid may accordingly also remove Zn2+ from the active site of the PPi-ase. It is suggested that in developing dental tissues alkaline phosphatase is not only associated with the transport of phosphate ions towards the mineralization front, but is also involved in the phosphorylation of organic macromolecules, a process activated the PPi-ase part of the enzyme.
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PMID:Possible functions of alkaline phosphatase in dental mineralization: cadmium effects. 165 1

1. Intracellular and whole-cell recordings were made from primary cultures of rat intermediate pituitary cells; beta-endorphin secretion was also measured by radioimmunoassay. The effects of dopamine receptor activation on hormone secretion, calcium currents and resting potassium conductance were compared. 2. Spontaneous sodium-dependent action potentials occurred in 82% of cells recorded with intracellular microelectrodes and 64% of cells recorded with whole-cell patch electrodes; the same proportion of cells showed spontaneous calcium-dependent depolarizations in the presence of tetrodotoxin. 3. Calcium currents recorded from holding potentials of -90 or -70 mV showed transient and sustained components, both of which activated at -40 mV and had similar current-voltage relations. Bay K 8644 (1 microM) increased both components by about 130% while nifedipine (1-10 microM) decreased them by a maximum of 30%. Nickel (500 microM) inhibited transient and sustained components by 68 and 50%; cadmium (100 microM) abolished the current. omega-Conotoxin (1 microM) reversibly inhibited the transient component by 26%. 4. The dopamine D2 receptor agonist, quinpirole (0.1-10 microM) inhibited transient and sustained components in all cells by a maximum of 40 and 25% respectively. Quinpirole did not alter the time course of the current. 5. Quinpirole (1-100 nM) hyperpolarized 90% of cells from which intracellular recordings were made and 55% of cells recorded from with whole-cell patch pipettes. Maximum hyperpolarization of 16 +/- 4 mV from a resting potential of -44 +/- 5 mV was observed with 100 nM-quinpirole; concentration producing half-maximal effect was 3 nM. The hyperpolarization resulted from an increase in potassium conductance. 6. Quinpirole (1-100 nM) decreased basal beta-endorphin secretion by 55% and abolished secretion stimulated by Bay K 8644 or isoprenaline; concentrations producing half-maximal inhibitions were 5-10 nM. Tetrodotoxin (1 microM), nifedipine (1 microM), nickel (500 microM) and cadmium (100 microM) did not alter basal or stimulated secretion although higher concentrations of cadmium did inhibit stimulated hormone release. 7. Pertussis toxin pre-treatment prevented all actions of quinpirole. 8. Thus, concentrations of quinpirole that abolished stimulated hormone secretion did not alter calcium currents; conversely, concentrations of calcium channel blockers that partially or completely inhibited calcium currents did not alter basal or stimulated secretion. These results may indicate that calcium influx through the voltage-dependent calcium channels measured in these experiments does not contribute significantly to hormone release from melanotrophs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopamine actions on calcium currents, potassium currents and hormone release in rat melanotrophs. 171 75

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

We have examined the action of GABA on the electrical, secretory and synthetic activities of rat and porcine intermediate lobe (IL) cells in primary culture. Chloride and calcium currents were investigated using patch-clamp techniques. A chloride current activated by 1-100 microM isoguvacine, a specific GABA-A agonist, and antagonised by bicuculline and SR 95103 was recorded at the whole cell and single channel level current. Whole cell calcium currents were investigated and shown to be reduced by 40 microM cadmium, zero external calcium and 10 microM baclofen, a specific GABA-B receptor agonist. Both GABA-B receptor activation and use of calcium deficient medium inhibited peptide release from IL cells. Finally, pro-opiomelanocortin (POMC) mRNA levels were measured using a hybridization technique. Removal of calcium from the culture medium or long-term (48 hr) incubation with 10 microM GABA or muscimol (a mixed GABA-A and GABA-B agonist) significantly reduced POMC mRNA levels.
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PMID:Ionic conductances related to GABA action on secretory and biosynthetic activity of pars intermedia cells. 243 3

The contribution of voltage-operated calcium (VOC) channels in the mechanism of release of alpha-melanocyte-stimulating hormone (alpha-MSH) from hypothalamic neurons was investigated using perifused rat hypothalamic slices. The stimulatory effect of potassium (50 mM) on alpha-MSH release was completely blocked by cadmium (1 mM) a calcium competitor which indifferently blocks T-, L-and N-type VOC channels. To determine the nature of calcium conductances involved in K+-evoked alpha-MSH release, we have investigated the effect of a VOC channel agonist and 3 antagonists on the secretion of the neuropeptide. Administration of synthetic omega-conotoxin fraction GVIA (1 microM), a peptide toxin which blocks both N- and L-type VOC channels, reduced by 33% K+-induced alpha-MSH release. In contrast, the 1,4-dihydropyridine (DHP) antagonist nifedipine, at concentrations up to 100 microM, did not affect the response of hypothalamic alpha-MSH neurons to depolarizing concentrations of KCl. In addition, the secretion of alpha-MSH induced by high K+ concentrations was not reduced by nifedipine (10 microM) in the presence of diltiazem (1 microM), a benzothiazepine derivative which increases the affinity of the DHP antagonist for L-type VOC channels. The DHP agonist BAY K 8644 (0.1-10 microM) did not modify the early phase of the response of alpha-MSH neurons to K+-induced depolarization. In contrast BAY K 8644 (1 or 10 microM) significantly prolonged the duration of K+-induced alpha-MSH release. This sustained release of alpha-MSH induced by BAY K 8644 (10 microM) was totally suppressed by nifedipine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of voltage-operated calcium channels in alpha-melanocyte-stimulating hormone (alpha-MSH) release from perifused rat hypothalamic slices. 254 28

p-Nitrophenyl phosphatase (p-NPP-ase) and inorganic pyrophosphatase (PPi-ase) activities originate from the same alkaline phosphatase enzyme. Only the PPi-ase site has zinc (Zn2+) as a cofactor. Cadmium (Cd2+) in concentrations from 10(-5) mol/l upwards inhibited the PPi-ase activity, but did not inhibit the p-NPP-ase activity at all. In mineralizing tooth germs Cd2+ may replace Zn2+, thereby changing the specific stereoconfiguration in the active centre needed for PPi-ase activity, but not that for p-NPP-ase activity.
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PMID:The effects of cadmium on the p-nitrophenyl phosphatase and inorganic pyrophosphatase activities of alkaline phosphatase in developing hamster tooth germs. 255 86

Extracellular recording in guinea-pig or mouse vas deferens or rat tail artery was used to study the effects of some pharmacological agents on the nerve terminal spike (NTS) and the secretion of a sympathetic co-transmitter (presumably ATP), as reflected in the excitatory junction current (EJC). A negative-going EJCi (i for inside) was assumed to reflect release from sites inside, and a positive-going EJCo (o for outside) release from sites outside the recording electrode. Passage into or out of the electrode seemed to be slow. Tetrodotoxin (TTX) in the outer medium blocked the NTS and ECJo as well as EJCi; TTX in the pipette blocked stimulus-evoked but not spontaneous EJCi. The dihydropyridine Ca2+ channel blocking agent, nifedipine, was without effect, but Cd2+ in the external medium blocked EJCo and also, by an effect apparently 'upstream' of varicosities, inhibited EJCi (i.e. release within the patch) but not the NTS. When present in the outer medium the alpha 2-adrenoceptor agonists, clonidine and xylazine, blocked both EJCo and EJCi, but not the NTS. The effects of clonidine were blocked by yohimbine, which in itself increased the EJCo by about 50%. Neuropeptide Y and met-enkephalin in the outer medium blocked EJCo; the effect of met-enkephalin was blocked by naloxone. The K+ channel blocking agents, tetraethylammonium and 4-aminopyridine, inside or outside the electrode, increased dramatically the size of EJCi or EJCo, respectively.
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PMID:Some pharmacological applications of an extracellular recording method to study secretion of a sympathetic co-transmitter, presumably ATP. 256 19

The possibility that divalent cations may antagonize opiate peptide analgesia and stress-induced analgesia was examined. Intracerebroventricular injection of low doses of Ca2+, Mn2+ and Mg2+ antagonized beta-endorphin and methionine-enkephalin analgesia. Ba2+ and Cd2+ were without effect. The ionophore, A23187, significantly antagonized beta-endorphin analgesia and the effect was increased when a low dose of Ca2+ was injected at the same time as the ionophore. Ethylene glycol tetraacetic acid (but not ethylenediamine tetraacetic acid) significantly potentiated endorphin analgesia. Stress-induced analgesia, as determined by increased tail-flick latencies following intraperitoneal injection of acetic acid, was effectively antagonized by naloxone, Ca2+ and Mn2+. The frequency of writhing following acetic acid injection was increased by both naloxone and divalent metal ions, again suggesting antagonism of endogenous opiates. These results confirm previous findings indicating that divalent metal ions (and especially Ca2+) may be involved in the actions of opiates.
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PMID:Modification of endorphin/enkephalin analgesia and stress-induced analgesia by divalent cations, a cation chelator and an ionophore. 682 Nov 93

A corticotropin-releasing hormone (CRH) and cAMP-responsive region (-236/-133) in the rat POMC gene promoter previously reported to confer CRH/cAMP responsiveness to heterologous reporter constructs has been characterized. DNAse footprint analysis revealed that multiple elements in this region were bound by nuclear proteins from the POMC expressing AtT20 cells. When these individual DNA elements were separately tested in heterologous reporter constructs for CRH induction, only one element, designated PCRH-RE (POMC CRH responsive element, -171/-160) was found to give strong CRH stimulation (5- to 7-fold). This element appears novel as to the possible binding factors, although it has homology to the mouse metallothionein metal regulatory element. Gel shift analyses of the PCRH-RE with AtT20 cell nuclear extracts showed marked stimulation of retarded nucleoproteins following CRH stimulation, suggesting that the possible binding factor(s) may mediate transcriptional regulation at this site. The activity of PCRH-RE binding protein was inhibited by divalent cations, with Cu2+ and Cd2+ being most effective; Zn2+ had no effect, indicating that this binding factor(s) is functionally distinct from the metallothionein metal regulatory element binding protein. A 2.6 kilobase cDNA clone encoding a protein (PCRH-REB-1) binding to this element was isolated by Southwestern screening of an AtT20 expression library with radiolabeled PCRH-RE oligonucleotides. This clone was used to isolate several other cDNA clones to determine the sequence corresponding to the entire coding region of the protein (PCRH-REB), which proved to be identical to a recently described DNA binding protein of the replication factor C complex, mRFC140/Mouse Southwestern. Primer extension and Northern blot analysis revealed that the size of the full length mRNA is about 4.9 kilobases. PCRH-REB mRNA expression is not restricted to corticotrophs but is present in a broad tissue distribution as evaluated by reverse transcription polymerase chain reaction analysis. A bacterially expressed beta-galactosidase-PCRH-REB-1 fusion protein was shown to bind PCRH-RE efficiently. Furthermore, binding of the PCRH-REB-1 fusion protein to the POMC CRH-responsive element was inhibited by divalent cations with similar sensitivities to those observed using AtT20 nuclear extracts. The predicted PCHR-REB protein sequence presents several interesting motifs: one p-Loop motif (ATP binding site), nine protein kinase A phosphorylation sites (implying a possible role in responding to the CRH-induced cAMP signal), and regions of homology to proteins involved in DNA replication and repair. PCRH-REB is, therefore, a potential transacting factor binding to a major CRH-responsive element in the POMC promoter.
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PMID:Characterization of a corticotropin-releasing hormone-responsive element in the rat proopiomelanocortin gene promoter and molecular cloning of its binding protein. 785 55

Arginine vasopressin (AVP) stimulates adrenocorticotropin (ACTH) release from pituitary corticotrophs by a mechanism dependent on extracellular calcium (Ca2+e). The involvement, in this response, of Ca2+ influx via L-type voltage sensitive Ca2+ channels (VSCC) was studied using cultured ovine anterior pituitary cells. Representatives of 3 chemically distinct classes of organic antagonists of L-type VSCC (methoxyverapamil (D600), nifedipine and diltiazem) and 2 inorganic blocking ions (Cd2+ and Co2+) were used. All of the blockers reduced AVP-stimulated ACTH release, but none caused complete inhibition. ACTH release in response to raised extracellular K+ concentration was also inhibited by these antagonists, with D600 and Cd2+ completely abolishing the response. These results indicate that there is a considerable, but not total, dependence on Ca2+ influx via L-type VSCC during the ACTH response to AVP in ovine corticotrophs.
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PMID:The effects of a chemically diverse range of calcium channel antagonists on the AVP-stimulated ACTH response in ovine corticotrophs. 795 9


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