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)

The 1,4-dihydropyridine BAY-K-8644 [methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate] acts as both a calcium channel agonist and antagonist by stimulating or inhibiting inward calcium current. In AtT-20 mouse pituitary tumor cells, BAY-K-8644 both stimulates and blocks adrenocorticotropin (ACTH) secretion. Because in several cell systems the cytoplasmic enzyme guanylate cyclase is activated, presumably by calcium entry, the effect of BAY-K-8644 on cyclic GMP (cGMP) synthesis in AtT-20 cells was assessed. BAY-K-8644 increased cGMP accumulation in a time-dependent manner. The concentrations of BAY-K-8644, however, required to increase cGMP formation were not associated with its stimulatory effects on secretion but rather with its ability to antagonize basal and (-)-isoproterenol-induced ACTH secretion. The inhibitory effect of BAY-K-8644 on ACTH secretion was not mimicked by 8-Br-cGMP. The cGMP response to BAY-K-8644 was not mimicked by the cationophore, A-23187, or depolarizing concentrations of K+. Other calcium channel antagonists such as nifedipine or verapamil had markedly smaller effects on cGMP formation compared to BAY-K-8644. Sodium nitroprusside and sodium azide both increased cGMP synthesis in AtT-20 cells and both inhibited, to a lesser extent than BAY-K-8644, both basal- and (-)-isoproterenol-stimulated ACTH release. The data suggest that BAY-K-8644 stimulates cGMP synthesis by binding to sites less accessible or poorly activated by other dihydropyridines, and that stimulation of guanylate cyclase is independent of inward calcium current.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:BAY-K-8644-stimulated cyclic GMP synthesis in mouse pituitary tumor cells. 241 44

The concentration of mRNA encoding proopiomelanocortin (POMC) was measured in AtT-20/D-16v cells, a clonal pituitary tumor cell line. Treatment of the cells with potassium (20 mM) or veratridine (10 microM) for 12, 24 and 48 h caused a time-dependent increase in the levels of POMC mRNA which became significant after 24 h. These effects were not seen in the presence of the sodium channel blocker tetrodotoxin (5 microM). In addition, the calcium channel blocker verapamil (10 microM) completely abolished the responses to either potassium or veratridine, whereas the calcium channel agonist Bay K 8644 (0.1 microM) potentiated the effect of potassium. Furthermore, the calcium channel blockers verapamil (10 microM) and nidefipine (1 microM) significantly decreased not only basal levels of POMC mRNA but also the increase of mRNA levels induced by corticotropin-releasing factor (CRF; 0.1 microM), 8-bromo-cAMP (1 mM) or cholera toxin (100 ng/ml). The drug-induced alterations in the mRNA POMC levels of the cells were, in each case, associated with similar alterations of immunoreactive beta-endorphin in the medium. These results indicate that membrane depolarization to activate sodium channels and calcium channels initiates an entry of calcium ions which triggers POMC gene expression in the AtT-20 cells. Moreover, calcium entry into the cells may exert a tonic stimulatory effect on POMC mRNA under basal conditions and may also contribute to the enhancing effect of CRF or cAMP on POMC mRNA in these cells.
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PMID:Influence of calcium ions on proopiomelanocortin mRNA levels in clonal anterior pituitary cells. 244 1

The effects of a non-narcotic analgetic methamizole and the calcium channel blocker verapamil on carrageenan hyperalgesia, release of beta-endorphin and synthesis of prostaglandin E2 (PGE2) were studied. It was found that a combined administration of analgin and verapamil prolonged the analgesic effect. Analgin stimulated release of beta-endorphin with the maximum coinciding in time with the peak of the analgesic effect. Against the background of the action of calcium ionophore A 23187 the combination of analgin with verapamil inhibited PGE2 synthesis more distinctly. The combination of these pharmacological agents is suggested to exert the effect both at different levels, central and peripheral, and on various cellular mechanisms involved in pain modulation.
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PMID:[Importance of endogenous opioids and prostaglandins in the action of analgin (metamizole) and verapamil]. 250 48

Rat adrenal glomerulosa cells labelled for 18 h with [3H]inositol responded to angiotensin II with a dose-dependent stimulation of the accumulation of inositol monophosphate, inositol bisphosphate and inositol trisphosphate. Addition of adrenocorticotropic hormone (ACTH) (10(-7)M) reduced the maximum responses without altering the EC50 values for angiotensin II. Thus, ACTH acted as a non-competitive inhibitor with respect to angiotensin II. No inhibition was observed in cells labelled for 2 h with [3H]inositol. Detailed examination of the inhibition showed that ACTH(1-24) was the most potent inhibitor, with ACTH(1-39) being 10-fold less potent. A mixture of alpha-melanocyte-stimulating hormone (alpha-MSH) (ACTH(1-13] and corticotropin-like intermediate lobe peptide (ACTH(18-39] was similarly inactive. ACTH(5-24) did not produce detectable inhibition. In terms of specificity, the receptor mediating ACTH inhibition of phosphatidylinositol turnover was similar to the receptor which mediated stimulation of aldosterone synthesis. Inhibition by ACTH was additive with inhibition produced by dibutyryl cAMP demonstrating that it was not mediated by rises in intracellular cAMP. ACTH inhibition also was additive with inhibition by the calcium channel blocker, nifedipine. These results demonstrate an interaction between ACTH receptors and angiotensin II receptors in adrenal glomerulosa cells at the level of their receptor-second messenger pathways.
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PMID:Adrenocorticotropic hormone inhibits angiotensin II-stimulated inositol phosphate accumulation in rat adrenal glomerulosa cells. 254 42

Acute or chronic cocaine administration exerts multiple behavioral and physiologic effects including stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. Pharmacologically, cocaine shares major properties with at least 2 classes of pharmaceuticals. It is a local anesthetic and also a potent psychomotor stimulant. The psychomotor stimulant properties of cocaine are thought to be related to its ability to modify the metabolism and the activity of many neurotransmitter systems, such as acetylcholine (ACh), serotonin (5-HT), norepinephrine (NE), and dopamine (DA). We and others have shown that all these neurotransmitters are potent stimulants of hypothalamic corticotropin-releasing hormone (CRH) secretion. The present study was undertaken to examine whether cocaine stimulates hypothalamic CRH secretion and whether or not such an effect is mediated by any of the above neurotransmitters. To accomplish this task, we employed a rat hypothalamic organ culture system, in which CRH secretion form single explanted hypothalami was evaluated by specific radioimmunoassay (iCRH). Cocaine stimulated iCRH secretion in a dose-dependent fashion with peak of activity at 10(-8) M. Isolated or simultaneous pharmacologic blockade of cholinergic (atropine plus hexamethonium), serotonergic (ritanserin), alpha-adrenergic (phentolamine) and/or dopaminergic (compound SCH 23390) receptor subtypes failed to inhibit cocaine-induced iCRH secretion. On the other hand, cocaine-induced iCRH secretion was inhibited by GABA, a potent inhibitor of CRH secretion, dexamethasone, verapamil, a calcium channel blocker, tetrodotoxin, a sodium channel blocker, and carbamazepine, an antiepileptic and antidepressive agent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cocaine stimulates rat hypothalamic corticotropin-releasing hormone secretion in vitro. 261 79

Adrenocorticotropic hormone (ACTH)1-24, ACTH4-10, corticosterone (CS) or arginine vasopressin (AVP) was administered subcutaneously to one day-old chicks immediately after learning a single trial passive avoidance task. Chicks were pretreated with 2 mM KC1 or 4 mM monosodium glutamate 5 min before learning. With KC1 or monosodium glutamate alone, no evidence of memory was observed on retention tests carried out as early as 5 min and as late as 24 h postlearning. However, the addition of ACTH1-24, ACTH4-10 or AVP to KC1-pretreated animals yielded normal retention levels up till 10 min, 10 min and 20 min after learning, respectively. Similar results were obtained with ACTH1-24 and AVP given to glutamate-pretreated birds. CS had no effect on KC1- or glutamate-induced amnesia. The calcium channel blocker, lanthanum chloride, also inhibited the formation of short-term memory, with amnesia still present as late as 24 h following learning. ACTH1-24, but not CS or AVP, yielded normal retention levels until 10 min postlearning in the presence of lanthanum chloride. Thus ACTH1-24 and AVP can overcome KC1 or glutamate inhibition of STM formation but will not prevent subsequent amnesia. The mechanisms underlying this action of ACTH1-24 and AVP are different. The possibility that the effect of ACTH1-24 is related to the role of calcium in STM formation is explored.
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PMID:Effect of stress-related hormones on short term memory. 286 68

Using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," one can identify and localize minute amounts of bioactive substances (including neurotransmitters), micro-organisms, toxic substances, or drugs, and, in addition, one can non-invasively image normal organs as well as screen for and image the distribution of specific types of cancer of specific internal organs without using any expensive instrumentation. One can also use this method to perform a qualitative analysis of neurotransmitters, neuromodulators, and hormones on different parts of the imaged organs. The molecule or substance being investigated is compared with a minute amount of a pure control reference substance, and if the substance identical to the control reference substance exists, then the electro-magnetic waves emitted by the identical substance will produce an electro-magnetic resonance phenomenon with the electro-magnetic waves of identical resonance frequency emitted by the control reference substance, and this resonance phenomenon is hypothesized to be the basis of the "Bi-Digital O-Ring Test Molecular Identification and Localization Method." The following substances have been used as control reference substances to identify and localize identical substances in vitro and in vivo: pure neurotransmitters (e.g. serotonin, beta-endorphin, methionine-enkephalin, norepinephrine, dopamine, L-dopa, substance P, etc.), as well as L-tryptophan and L-tyrosine; cholesterol; steroid hormones (including aldosterone, corticosterone, cortisol, progesterone, testosterone, etc.); peptide hormones; microscopic slides of normal organs; microscopic slides of specific cancer cells of specific organs (e.g. adenocarcinoma of the head of the pancreas, adenocarcinoma of the descending colon, etc.); microscopic slides of pure micro-organisms; toxic substances (e.g. lead, mercury, KCN); drugs (including non-steroidal anti-inflammatory drugs, antibiotics, beta-blockers, calcium channel blockers, etc.); and antibodies against specific substances or micro-organisms. An intensive network of serotonin and L-tryptophan was discovered, by using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," in different parts of the body. In general, in painful areas, frequently serotonin is markedly reduced, L-tryptophan is markedly increased, and substance P is markedly increased, while in non-painful areas, serotonin is markedly increased, L-tryptophan is markedly decreased, and substance P is markedly decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:"Bi-digital o-ring test molecular identification and localization method" and its application in imaging of internal organs and malignant tumors as well as identification and localization of neurotransmitters and micro-organisms--Part 1. 287 19

The effect of barium and potassium on the secretion and biosynthesis of enkephalin in bovine chromaffin cells, and prolactin and beta-endorphin in rat anterior pituitary cells, was examined to determine whether calcium-dependent secretion and biosynthesis are mediated by the same or by different calcium targets within the neuroendocrine cell. In the presence of 1.8 mM calcium, barium and potassium stimulated the secretion of all three peptides over 30 min, and increased the levels of proenkephalin and prolactin mRNA in 24 hr. These effects were inhibited by the calcium channel blocker D600. When the extracellular calcium concentration was lowered to 0.1 mM or less, secretion elicited by potassium was blocked, whereas secretion elicited by barium was enhanced, indicating that barium wholly substitutes for extracellular calcium in mediating peptide secretion. On the other hand, stimulation of proenkephalin and prolactin mRNA by both potassium and barium was inhibited when the extracellular calcium concentration was reduced. We conclude that calcium acts at two different intracellular targets to activate secretion versus biosynthesis of both enkephalin and prolactin. This appears to be the first report in which two different calcium-dependent processes in the intact cell are distinguished by a calcium ion agonist. Calcium-dependent processes such as protein phosphorylation, protein translocation, and enzyme activation may thus be related to events in the intact cell such as peptide synthesis and secretion on the basis of selective stimulation by barium.
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PMID:Barium distinguishes separate calcium targets for synthesis and secretion of peptides in neuroendocrine cells. 295 45

Atrial natriuretic factor (ANF) inhibits basal and stimulated aldosterone synthesis in adrenal glomerulosa cells. ANF probably acts through specific membrane receptors. Alterations in cyclic GMP and cyclic AMP levels do not account for ANF's inhibitory effect. ANF does not block angiotensin II (AngII) receptors nor does it interfere with phosphoinositide metabolism or calcium movements stimulated by adrenal agonists. ANF does not inhibit protein synthesis nor does it work by inhibiting NA+,K+-ATPase or depleting cell potassium. ANF decreases conversion of endogenous cholesterol to pregnenolone, the step stimulated by adrenocorticotropin and AngII. ANF does not affect the conversion of 20-alpha-hydroxycholesterol, which easily penetrates mitochondrial membranes to the site of the cholesterol side-chain cleavage enzyme. These results suggest that ANF inhibits the ability of endogenous cholesterol to reach or interact with the side-chain cleavage enzyme. ANF does not act like a calcium channel-blocking agent. However, ANF is less effective at high-calcium concentrations, which suggests that it may inhibit a step that calcium stimulates. Understanding ANF action will probably require identification of the specific biochemical changes (mediators) that it induces. Parallel efforts to understand how other agents stimulate steroidogenesis (particularly in the areas of protein synthesis, protein phosphorylation, and cholesterol movements) will further this understanding.
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PMID:Inhibition of aldosterone synthesis by atrial natriuretic factor. 301 92

The divalent cation barium was used to study the role of calcium in coupling neuropeptide secretion and biosynthesis following secretagogue stimulation of bovine chromaffin cells. Barium chloride (0.1-2.5 mM) stimulated in a dose-dependent manner the secretion of met-enkephalin (up to 20% of intracellular peptide content) and increased the total amount (cell plus medium content) of met-enkephalin and vasoactive intestinal polypeptide (VIP) 2- to 3-fold after 72 hours. A greater than six-fold increase in proenkephalin mRNA (mRNA(enk)) was observed by 24 hours following barium stimulation. The voltage-sensitive calcium channel blocker D600 inhibited the barium-stimulated secretion of enkephalin and blocked the stimulation of VIP biosynthesis and mRNA(enk). Reducing calcium in the medium resulted in an enhancement of barium-stimulated release of both peptides, but blocked the induction of their biosynthesis. The data indicate that calcium targets involved in secretion can be activated by barium or calcium while calcium targets involved in biosynthesis specifically require calcium. It is therefore proposed that pathways leading to peptide secretion and biosynthesis in the adrenal diverge just after secretagogue-stimulated calcium influx.
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PMID:Calcium requirements for barium stimulation of enkephalin and vasoactive intestinal peptide biosynthesis in adrenomedullary chromaffin cells. 336 36


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