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)

This study describes effects of ACTH1-24 and beta-endorphin on brain polyphosphoinositide metabolism in vitro. The interconversion of these polyanionic phospholipids was studied by incubation of a lysed synaptosomal fraction with [gamma-32P]ATP. Of the membrane phospholipids only PA, DPI and TPI became labeled. The reference peptide ACTH1-24 stimulated the formation of TPI and inhibited the production of PA. For effects on TPI formation both the sequences ACTH5-7 and ACTH10-16 were needed. Effects on PA formation required the sequences ACTH7-10 and ACTH10-16. The basic amino acids in ACTH10-16 seemed to be of crucial importance for the peptide effects. A stimulatory effect on DPI was visible when ACTH was shortened from the N-terminus, and the essential information was in ACTH7-10. beta-endorphin inhibited PA formation and this effect was abolished by C-terminal shortening to gamma-endorphin. Other fragments of the C-terminus of beta-LPH, including the enkephalins, were ineffective. It is concluded that the structure-activity relationship on TPI/PA formation correlates with a similar relationship obtained on excessive grooming behavior in vivo. A possible correlation between the effects on polyPI metabolism and opiate-like effects, and effects on extinction of active avoidance behavior in vivo is discussed.
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PMID:Modulation of brain polyphosphoinositide metabolism by ACTH and beta-endorphin: structure-activity studies. 626 9

1. Effects of corticotropin-(1--24)-tetracosapeptide on the endogenous phosphorylation of proteins and lipids were studied in a membrane/cytosol fraction prepared from a lysed crude mitochondrial/synaptosomal fraction. 2. The labelling of proteins and lipids was monitored by incubation of the subcellular fraction for 10s with [gamma-32P]ATP. 3. The phosphorylation of proteins was dose-dependently inhibited by the peptide (40% of control incubations at 100 microM-corticotropin). 4. Of the membrane phospholipids only phosphatidylinositol phosphate, phosphatidylinositol bisphosphate and phosphatidic acid became labelled. Corticotropin dose-dependently increased the formation of phosphatidylinositol bisphosphate and inhibited the production of phosphatidic acid (470% and 50% respectively of control incubations, at 100 microM of the peptide) and had no effect on phosphatidylinositol phosphate. 5. Phosphatase activity was observed to act on phosphatidylinositol bisphosphate, phosphatidylinositol phosphate and phosphoprotein but not on phosphatidic acid. 6. Corticotropin interacted with the kinases rather than with the phosphatases. 7. The formation of phosphatidylinositol bisphosphate and phosphatidic acid was maximal at 1--10mM-Mg2+ in the absence of Ca2+, and the production of phosphatidylinositol phosphate was maximal at 30mM-Mg2+. 8. The basal value of lipid phosphorylation decreased with increasing Ca2+ concentration. 9. Ca2+ abolished the effect of corticotropin on phosphatidylinositol bisphosphate formation (470%, 190% and 100% of control incubations at respectively 0, 0.1 and 1 mM-Ca2+). 10. The data provide evidence that the effects of corticotropin on protein phosphorylation and on polyphosphoinositide metabolism in brain membranes are related.
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PMID:Corticotropin-(1--24)-tetracosapeptide affects protein phosphorylation and polyphosphoinositide metabolism in rat brain. 627 27

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

To study the relative roles of sodium (Na+) and calcium ions (Ca2+) in the response of adrenal glomerulosa cells, we investigated the effects of different Na+ concentrations in the incubation media and the actions of substances that interfere with Ca2+ fluxes. Basal aldosterone secretion and response to angiotensin II (AII), adrenocorticotropic hormone (ACTH), or potassium (K+) were dependent on extracellular Na+ concentration. Veratridine, a Na+ channel opener that dissipates Na+ gradients, blocked the stimulated steroidogenic response. Mersalyl acid and tetracaine, which are potent Ca2+ antagonists, blocked the effects of aldosterone secretagogues. Divalent cations with Ca2+ antagonistic action such as manganese M(n2+), nickel (Ni2+), and cobalt (Co2+) blocked the aldosterone secretory response to AII, ACTH, and K+. Barium (Ba2+) and strontium (Sr2+), known to mimick Ca2+ effects, increased or did not affect responses of the glomerulosa cells. Sodium vanadate, an inhibitor of ATP-dependent Ca2+ translocation, did not alter the stimulated aldosterone responses. Trifluoperazine (10(-6) M), an inhibitor of calmodulin, blocked AII and K+-induced aldosterone secretion, but was partially effective on ACTH-stimulated aldosterone output only at a concentration of 10(-5) M. The actions of ouabain on aldosterone biosynthesis were similarly affected by all these drugs. Thus, both extracellular Na+ and Ca2+ appear to play a role in the steroidogenic response of isolated glomerulosa cells. The intracellular action of Ca2+ may involve a calmodulin-like protein. The effects of ACTH are only partially dependent on Ca2+ as a second intracellular messenger.
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PMID:Relative roles of sodium and calcium ions in the steroidogenic response of isolated rate adrenal glomerulosa cells. 627 6

A significant proportion of the steroidogenic response of isolated rat adrenocortical cells to dibutyryl cyclic AMP does not require extracellular calcium, and this component is profoundly depressed by low concentrations of the putative calcium antagonist, TMB-8. The inhibition is reversed by either the readdition of calcium or the calcium ionophore A23187. The steroidogenic response to pregnenolone, whose mode of action does not require calcium, was not depressed by TMB-8. Corticotropin (ACTH)-induced steroidogenesis, which requires extracellular calcium, was markedly depressed by TMB-8, although enhanced cyclic AMP formation is only slightly depressed by this drug. Adrenal cortical microsomes possess an ATP-dependent 45calcium (45Ca2+) uptake system which responded to EGTA with a rapid efflux of 45Ca2+; EGTA-induced calcium efflux from this microsomal fraction was markedly reduced by a concentration of TMB-8 that blocked dibutyryl cyclic AMP-evoked steroidogenesis. TMB-8 produced a smaller but significant reduction of EGTA-facilitated 45Ca2+ efflux from a mitochondrial-enriched fraction. We interpret these results to mean that TMB-8 blocks the steroidogenic effect of dibutyryl cyclic AMP by interfering with the mobilization of a cellular pool of calcium that is probably localized to the endoplasmic reticulum. The physiological implications of these findings in relation to the complex interactions between calcium and cyclic AMP in adrenal steroidogenesis are discussed.
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PMID:Inhibition of dibutyryl cyclic AMP induced steroidogenesis in rat adrenocortical cells by the putative calcium antagonist TMB-8. 628 80

This study on the phosphorylation in vivo of membrane proteins in cerebral cortices of infant rats reports the identification of the adrenocorticotropin (ACTH)-sensitive phosphoprotein B-50 as one of the substrate proteins that are rapidly phosphorylated in vivo following intracisternal administration of 2 mCi [32P]orthophosphate. Rats were sacrificed 30 min after isotope injection. A fraction enriched in membranes, designated neural membranes (NM), was isolated from the cerebral cortices according to the procedure used for preparation of synaptic plasma membranes (SPM) from adult brain. This NM fraction was characterized by electron microscopy. The proteins of NM were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Numerous protein bands of NM in infant rat brain were phosphorylated in vivo. Attention was focussed on the 32P-labeled protein bands in the molecular weight range of 47K-67K. In this region one phosphoprotein band (MW 48K) was more highly labeled than the other bands. The electrophoretic behavior of three of these labeled bands, designated a, c, and e (MW 48K, 55K, and 62K, respectively) was compared with that of protein bands that were phosphorylated in vitro in cerebral membranes isolated from noninjected infant rats. The effects of ACTH1-24 and cyclic AMP in the in vitro system were also studied to probe for the presence of specific membrane proteins known to be sensitive to these modulators. On incubation of NM with [gamma-32P)ATP in the presence and absence of ACTH1-24 in vitro, phosphorylation of a 48K protein band was inhibited in a dose-dependent fashion by the neuropeptide. Two-dimensional electrophoretic separation of NM proteins labeled in vivo indicated that the 48K band had an isoelectric point of 4.5, identical to that of the ACTH-sensitive B-50 protein previously identified. Cyclic AMP stimulated phosphorylation in vitro of two protein bands (MW 55K and 59K) in NM preparations. This result indicates that the in vivo labeled band c may correspond to the cyclic AMP-sensitive 55K protein, whereas phosphoprotein band e, labeled in vivo, appears to be different from the cyclic AMP-sensitive 59K protein band. These observations indicate that neural membranes isolated from infant rat cerebral cortices contain a variety of proteins that can be phosphorylated in vivo. Several of these, for example, the 48K protein band, have the properties of synaptic plasma membrane proteins of adult rat brain that have been characterized by their sensitivity to neuromodulators in endogenous phosphorylating systems in vitro.
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PMID:Characterization of infant rat cerebral cortical membrane proteins phosphorylated in vivo: identification of the ACTH-sensitive phosphoprotein B-50. 628 76

The hypothesis that lipolytic hormones reduce the mitochondrial electrical potential in rat white adipocytes via free fatty acids (FFA) was examined. Hormonal effects on plasma and mitochondrial membrane potentials were evaluated with [3H]triphenylmethylphosphonium (TPMP+) and 86Rb+. FFA generation was controlled by varying medium albumin concentrations. In 4.0% albumin buffer, adrenocorticotropin or l-epinephrine increased intracellular FFAs, produced cellular TPMP+ efflux, ATP depletion, release of FFAs and glycerol, and no change in 86Rb+ distribution. In 0.5% albumin buffer, greater intracellular FFA accumulation accompanied greater TPMP+ and ATP depletion, significant loss of cell-associated 86Rb+, and a concomitant inhibition of FFA and glycerol release. Exogenous addition of FFAs mimicked the effect of hormones on adipocyte TPMP+ distribution. TPMP+ and 86Rb+ uptake into adipocyte "ghosts" were unaffected by hormones. We suggest that mitochondrial membrane depolarization is a metabolic response to hormones via FFA accumulation by white adipocytes. The additional hormonal effects that were observed in 0.5% albumin buffer may be related to inhibition of lipolysis secondary to intracellular ATP depletion.
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PMID:Hormones modulate adipocyte membrane potential ATP and lipolysis via free fatty acids. 631 Oct 25

Effects of the neuropeptide corticotropin-(1-24)-tetracosapeptide (ACTH) on the endogenous and exogenous phosphorylation of lipids and endogenous phosphorylation of proteins were investigated in microsomes and a 110,000 X g supernatant fraction [30-50% (NH4)2SO4 precipitate; ASP 30-50] obtained from rabbit iris smooth muscle. Subcellular distribution studies revealed that both of these fractions are enriched in diphosphoinositide (DPI) kinase. The 32P labeling of lipids and proteins was measured by incubation of the subcellular fractions with [gamma-32P]ATP. The labeled lipids, which consisted of triphosphoinositide (TPI), DPI, and phosphatidic acid (PA) were isolated by TLC. The microsomal and ASP 30-50 fractions were resolved into six and nine labeled phosphoprotein bands, respectively, by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The basal labeling of both lipids and proteins was rapid (30-60 s), and it was dependent on the presence of Mg2+ in the incubation medium; in general it was inhibited by high concentrations (greater than 0.2 mM) of Ca2+. ACTH stimulated the labeling of TPI and inhibited that of PA in a dose-dependent manner, with maximal effect observed at 50-100 microM of the peptide. ACTH appears to increase TPI labeling by stimulating the DPI kinase. Under the same experimental conditions ACTH (100 microM) inhibited significantly the endogenous phosphorylation of six microsomal phosphoproteins (100K, 84K, 65K, 53K, 48K, and 17K). In the ASP 30-50 fraction, ACTH inhibited the phosphorylation of three phosphoproteins (53K, 48K, and 17K) and stimulated the labeling of six phosphoprotein bands (117K, 100K, 84K, 65K, 42K, and 35K).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of corticotropin-(1-24)-tetracosapeptide on polyphosphoinositide metabolism and protein phosphorylation in rabbit iris subcellular fractions. 631 87

Fractions enriched in plasma membranes were prepared from the Y1 mouse adrenocortical tumor cell line and were characterized with respect to adenylate cyclase activity. Optimal requirements of the adenylate cyclase system for guanyl nucleotides. Mg2+, ATP, and corticotropin (ACTH) were determined. The sensitivity of the adenylate cyclase system to ACTH in plasma membrane fractions was comparable with that observed in isolated intact cells. Polycations such as poly-L-arginine and histone competitively inhibited the action of ACTH, supporting the view that the affinity of ACTH for the adenylate cyclase system is determined by the basic core of amino acids at residues 15-18. ACTH was at least one order of magnitude more potent than ACTH in stimulating adenylate cyclase activity in plasma membrane fractions.
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PMID:Adenylate cyclase activity in Y1 mouse adrenocortical tumor cells: some properties of the enzyme associated with purified plasma membrane fractions. 631 50

Rat erythrocyte ghosts containing 45Ca++, EGTA, ATP and Pipes buffer (pH 7.2) were prepared for studying opioid effects on Ca++ flux. Ethylketocyclazocine and dynorphin 1-13 (dynorphin) dose-dependently inhibited La+++-sensitive outward 45Ca++ movement at nM concentrations and the effect was naloxone reversible. Morphine and beta-endorphin were also effective at higher concentrations, whereas levorphanol and leu-enkephalin were ineffective. None of the opioids studied inhibited 45Ca++ inward movement. Based on these findings, it is concluded that rat erythrocyte possesses k-type opioid receptors through which the Ca++-pump may be inhibited.
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PMID:Possible inhibition of Ca++ pump of rat erythrocyte ghosts by opioid k agonists. 631 22


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