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)

Intraperitoneal injection of maximally effective doses of corticotropin(1-24) [ACTH(1-24)] provoked maximal increases in rat adrenal phospholipids as follows: phosphatidic acid within 1.5-2 min, phosphatidylinositol and phosphatidylglycerol within 4-6 min, and polyphosphoinositides and corticosterone within 5-15 min. Continued maximal adrenal stimulation by ACTH(1-18) treatment caused sustained increases in adrenal phosphatidic acid, phosphatidylinositol, phosphatidylglycerol, polyphosphoinositides, and corticosterone. Treatment with cycloheximide during this steady-state caused rapid decreases in all of these substances to basal levels. The observed half-lives of adrenal phosphatide acid, phosphatidylinositol, polyphosphoinositides, phosphatidylglycerol, and corticosterone during cycloheximide inhibition were 0.15, 1.0, 1.7, 3.3, and 3.5 min, respectively. Calculated production rates during maximal ACTH stimulation were 1060, 991, 90, 34, and 41 nmol/g of tissue per min, respectively. These findings suggest that (i) an initial effect of ACTH on de novo synthesis of phosphatidic acid can account for all subsequently observed increases in other phospholipid derivatives of CDP-diacylglycerol, (ii) a labile protein is required for the ACTH-induced increase in phosphatidic acid, (iii) the phosphatidate leads to polyphosphoinositide-polyglycerophospholipid pathway is rapidly and dramatically responsive to hormonal stimulation, (iv) changes in steroidogenesis correlate well with changes in this phospholipid pathway, and (v) stimulation of this pathway is rapidly reversible.
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PMID:Kinetic aspects of cycloheximide-induced reversal of adrenocorticotropin effects on steroidogenesis and adrenal phospholipids in vivo. 626 Dec 46

We studied the effects of adrenocorticotropin (ACTH) and cycloheximide on adrenal enzymes involved in phosphatidate synthesis. Treatment of rats in vivo with ACTH induced a rapid increase in phosphatide synthesis from diglyceride and ATP in adrenal homogenates, and cycloheximide treatment prevented this increase if given before ACTH and rapidly reversed the increase if given after ACTH. The stimulatory effect of ACTH appeared to be largely due to an increase in diglyceride substrate, as kinase activity was not altered. The inhibitory effect of cycloheximide, on the other hand, appeared to be due to a decrease in diglyceride kinase activity. Neither ACTH nor cycloheximide treatment had any effect on the activity of glycerol-3'-phosphate acyltransferase or phosphatidate phosphatase. Our findings suggest that (a) ACTH increases the flow of phospholipid (and their levels) throughout the entire circular pathway, i.e., phosphatidate leads to CDP-diacylglycerol leads to inositides leads to diglycerides leads to phosphatidate, and (b) a labile protein may serve to allow entry into a recycling of diglyceride in this pathway. In addition, since cycloheximide blocked carbachol-induced increases in pancreatic and salivary glandular phosphatidate synthesis resulting from phosphatidylinositol hydrolysis and consequent diglyceride generation, the putative labile protein may have widespread importance.
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PMID:Effects of adrenocorticotropin and cycloheximide on adrenal diglyceride kinase. 627 34

1. Parotid plasma membrane nonpump low-affinity Ca(2+)-ATPase, which possesses high-affinity (Ca2+ + Mg2+)-ATPase activity, was characterized. 2. Purified Ca(2+)-ATPase hydrolyzed the nucleoside triphosphates, GTP, ITP, CTP, UTP, TTP (67-93% of ATP) and nucleoside diphosphates, ADP, GDP, IDP, CDP, TDP (12-40% of ATP) but not AMP and p-NPP. 3. The maximum activities of Ca(2+)- and (Ca2+ + Mg2+)-ATPases were obtained in the presence of 1 mM and 0.13 microM Ca2+, respectively. 4. The Km values for Ca2+ in Ca(2+)- and (Ca2+ + Mg2+)-ATPases were 0.2 mM and 22 nM, respectively. 5. The activities of both Ca(2+)- and (Ca2+ + Mg2+)-ATPases were found in the right-side-out-vesicles obtained from the plasma membrane-rich fraction. 6. These features suggest that Ca(2+)-ATPase is an ecto-Ca(2+)-dependent nucleoside triphosphatase.
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PMID:The possibility that Ca(2+)-ATPase from the plasma membrane-rich fraction of bovine parotid gland is ecto-Ca(2+)-dependent nucleoside triphosphatase. 806 15

This study investigates the influence of possible stress due to housing in Bolman cages on antinociception and on respiratory depression following opioid administration. To evaluate the functional role of this stressor and to modulate it, rats were subcutaneously pretreated with the anxiolytic chlordiazepoxide (CDP; 10 mg/kg) or saline (SAL) before the immobilization in the Bolman cages and before the intravenous administration of small doses of morphine (MOR), sufentanil (SUF), or vehicle (VEH). Antinociception, respiratory impairment and stress were evaluated by means of the tail-flick latency, blood gas analysis, and serum corticosterone (CS), adrenocorticotropic hormone (ACTH), and prolactin (PRL) determinations. The results demonstrated that 10 mg/kg CDP did not alter the antinociceptive effects of low doses of morphine and sufentanil. CDP pretreatment differentially affected the various blood gas parameters. Compared to vehicle pretreatment, there was a larger decrease in PaO2 following MOR and SUF in the CDP-pretreated rats. The effects were most pronounced at the lowest doses of both opioids. A CDP potentiation was also observed for the short-lasting raises in PaCO2 with the lowest concentrations of the opioids. At higher concentrations of the opioids, CDP was without any effect. With regard to the stress hormones, immobilization and an intravenous injection resulted in increases in CS and PRL in both CDP- and VEH-pretreated rats. ACTH did not change in these controls. SUF prevented the CS raises independent of a CDP pretreatment, while ACTH only increased in the SUF plus CDP groups, pointing to a stress-reducing effect of SUF. Also, MOR without CDP prevented the increases in CS, but the opioid intrinsically increased ACTH. These results indicate that restraint in Bolman cages in the present setup, with animals recovering for several hours in these cages after being equipped with an arterial catheter, is stressful but without any significant effect on the opioid-induced antinociception. Pretreatment with an anxiolytic benzodiazepine only minimally affected the outcome of the opioids on respiratory depression and pointed to a stress-reducing effect of low doses of the opioids, especially sufentanil.
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PMID:Effects of chlordiazepoxide on opioid-induced antinociception and respiratory depression in restrained rats. 951 69

The protein phosphatase inhibition assay for okadaic acid, the major DSP toxin, modified to use the fluorescence substrates methylumbelliferyl phosphate (MUP) and fluorescein diphosphate (FDP), was compared to the assay using p-nitrophenylphosphate (p-NPP) and the bioluminescence assay using luciferin phosphate (L-P). Under the standard assay conditions used okadaic acid inhibited the enzyme activity dose-dependently with IC50 values of 1.5 nM (MUP) and 1.2 nM (FDP). This compares to IC50 values of 0.9 and 6 nM using L-P and p-NPP respectively. CDP-star, a chemiluminescence substrate, was not hydrolysed by the enzyme. Decreasing the enzyme concentration lowered the IC50 for the colorimetric method (IC50=2 nM [p-NPP], 0.75 nM enzyme) but no shift was observed with fluorimetry. However at enzyme concentrations < 1.5 nM (standard assay) the error margin was too great for routine analysis. The method using fluorimetry allowed detection of okadaic acid concentrations to levels < or = 1 microg/100 g of mussel tissue which is well below the limit of 20 microg/100 g (mouse bioassay) set by some regulatory agencies. Determination of the toxin content in naturally contaminated mussels in three separate experiments gave coefficients of variance ranging from 16 to 29% (MUP) and from 8 to78% (p-NPP). Multicomparison studies showed that concentrations of okadaic acid in naturally contaminated mussel samples determined by fluorescence generally agreed with those obtained using ELISA and LC-MS procedures, and with the mouse bioassay. However using the mouse bioassay as the standard, values determined by the ELISA, PP-2A and LC-MS all scored false negative results compared to those for the mouse bioassay in the range 20-40 microg/100 g mussel, and at the limit of the mouse bioassay the values by the other three methods were substantially less. With few exceptions the methods scored okadaic acid with highest to lowest values in the following order: mouse bioassay > ELISA > PP-2A > LC-MS. The fluorimetric assay was both more sensitive and accurate than the colorimetric assay (the latter showed a propensity towards false positives in the region 20 microg/100 g), and the moderate increase in equipment cost appears to be outweighed by the performance of the method.
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PMID:Evaluation of the fluorometric protein phosphatase inhibition assay in the determination of okadaic acid in mussels. 1034 Aug 30

In the present study, we investigated the effect of intracerebroventricular (i.c.v.) administration of cytidine-5'-diphosphate (CDP) choline on plasma adrenocorticotropin (ACTH), serum growth hormone (GH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in conscious rats. The involvement of cholinergic mechanisms in these effects was also determined. In basal conditions, CDP-choline (0.5, 1.0 and 2.0 micromol, i.c.v.) increased plasma ACTH levels dose- and time-dependently, but it did not affect the TSH, GH, FSH and LH levels. In stimulated conditions, i.c.v. administration of CDP-choline (1 micromol, i.c.v.) produced an increase in clonidine-stimulated GH, thyrotyropin-releasing hormone (TRH)-stimulated TSH, LH-releasing hormone (LHRH)-stimulated LH, but not FSH levels. Injection of equimolar dose of choline (1 micromol, i.c.v.) produced similar effects on hormone levels, but cytidine (1 micromol, i.c.v.) failed to alter plasma levels of these hormones. Pretreatment with hemicholinium-3, a neuronal high affinity choline uptake inhibitor, (20 microg, i.c.v.) completely blocked the observed hormone responses to CDP-choline. The increase in plasma ACTH levels induced by CDP-choline (1 micromol, i.c.v.) was abolished by pretreatment with mecamylamine, a nicotinic receptor antagonist, (50 microg, i.c.v.) but not atropine, a muscarinic receptor antagonist, (10 microg, i.c.v.). The increase in stimulated levels of serum TSH by CDP-choline (1 micromol, i.c.v.) was blocked by atropine but not by mecamylamine pretreatment. However, CDP-choline induced increases in serum GH and LH levels were greatly attenuated by both atropine and mecamylamine pretreatments. The results show that CDP-choline can increase plasma ACTH and produce additional increases in serum levels of TSH, GH and LH stimulated by TRH, clonidine and LHRH, respectively. The activation of central cholinergic system, mainly through the presynaptic mechanisms, was involved in these effects. Central nicotinic receptors solely mediated the increase in plasma ACTH levels while the activation of central muscarinic receptors was involved in the increase in TSH levels. Both muscarinic and nicotinic receptor activations, separately, mediated the increases in serum GH and LH levels after CDP-choline.
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PMID:CDP-choline increases plasma ACTH and potentiates the stimulated release of GH, TSH and LH: the cholinergic involvement. 1548 72