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)

Forskolin, an activator of adenylate cyclase, stimulates adrenocorticotropin (ACTH) release and increases proopiomelanocortin mRNA levels in anterior pituitary cells by enhancing cyclic AMP (cAMP)-dependent protein kinase activity. The phorbol ester phorbol 12-myristate 13-acetate (PMA) evokes these same responses from anterior pituitary cells by activating protein kinase C. Both protein kinases most likely induce their cellular effects by catalyzing the phosphorylation of specific proteins. To elucidate the mechanisms by which cAMP-dependent protein kinase and protein kinase C promote ACTH secretion and synthesis, the phosphoproteins regulated by forskolin and PMA were identified in the cell line AtT-20, which consists of a homogeneous population of corticotrophs. Phosphoproteins were analyzed in different subcellular fractions by two-dimensional polyacrylamide gel electrophoresis and autoradiography. Forskolin increased phosphate incorporation into two proteins in the cytoplasmic fraction of 24 kilodaltons (kd) (pI 6.8) and 40 kd (pI 5.8), two proteins in the plasma membrane fraction of 32 kd (pI 8.3) and 60 kd (pI 8), and one protein in the nuclear fraction of 20 kd (pI 8.7). Insertion of the inhibitor of cAMP-dependent protein kinase into the AtT-20 cells, using a liposome technique, blocked the rise in phosphate incorporation induced by forskolin. PMA also stimulated phosphate incorporation into proteins in AtT-20 cells. PMA increased the phosphorylation of three cytoplasmic proteins of 25 kd (pI 7.6), 40 kd (pI 5.8), and 40 kd (pI 8.1) as well as two membrane proteins of 32 kd (pI 8.3) and 60 kd (pI 8) and one nuclear protein of 20 kd (pI 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein phosphorylation induced by phorbol esters and cyclic AMP in anterior pituitary cells: possible role in adrenocorticotropin release and synthesis. 253 66

We have examined the effects of a biologically active tumor promoting phorbol ester (phorbol 12-myristate, 13-acetate (PMA] which activates protein kinase C (PKC) on melanotropin receptor function and cell growth in the M2R mouse melanoma cell clone. Treatment of M2R cells with PMA resulted in a significant loss of beta-MSH binding. The effect was both time- and concentration-dependent. The inhibition of beta-MSH binding resulted from a decrease (greater than 85%) in active membranal receptors available on the external cell surface and not from either enhanced internalization or change in the binding affinity. Agonist-stimulated cyclic AMP accumulation was profoundly increased in a non-selective manner following short-term incubation (3 h) with PMA. This effect was completely reversed during long-term (72-96 h) incubation with the tumor promoting agent. Long-term culturing of M2R cells with PMA resulted in enhanced (+50%) proliferation of the melanoma cells. This enhancement was blocked by the addition of agents which stimulate the production of cAMP. Hence, phorbol esters are powerful growth promoters in transformed melanocytes and our findings indicate that the effects of melanotropins are selectively impaired during the process of growth promotion.
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PMID:Phorbol ester impairs melanotropin receptor function and stimulates growth of cultured M2R melanoma cells. 254 Sep 97

There are controversial reports in the literature concerning the effects of opioids on superoxide (O2-) formation in phagocytes, these agents being either inhibitory or stimulatory. We re-examined this issue and compared the effects of the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), phorbol myristate acetate (PMA), ATP, platelet activating factor (PAF), cytochalasin B (CB) and prostaglandin E1 (PGE1) with those of various opioids on O2- formation in human neutrophils and HL-60 leukemic cells under defined experimental conditions. In the presence of CB, fMet-Leu-Phe and PAF concentration-dependently activated O2- formation in neutrophils with EC50 values of 20 nM and 100 nM, respectively. In the absence of CB, fMet-Leu-Phe and PAF were much less effective. PAF synergistically enhanced O2- formation induced by fMet-Leu-Phe. ATP at a concentration of 100 microM and the opioids, methionine enkephalin, beta-endorphin, dynorphin, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, [D-Ala2-D-Leu5]-enkephalin and morphine at concentrations between 10 pM to 1 microM did not activate O2- formation. ATP but not beta-endorphin potentiated fMet-Leu-Phe-induced O2- formation. O2- formation induced by a maximally stimulatory concentration of PMA (100 ng/ml) was enhanced by fMet-Leu-Phe but was unaffected by methionine enkephalin or PGE1. PMA at a non-stimulatory concentration (2 ng/ml) potentiated the effect of fMet-Leu-Phe but did not induce responsiveness to PAF, ATP or beta-endorphin. PGE1 strongly inhibited fMet-Leu-Phe-induced O2- formation, whereas morphine, methionine enkephalin and the opioid antagonist, naloxone, were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of effect of opioid peptides, morphine and naloxone on superoxide formation in human neutrophils and HL-60 leukemic cells. 255 28

Graded levels of hydrocortisone 21-acetate (HYD) (0, 18, 16 and 24 mg/kg BW) were injected into nursing piglets every other day (Exp. 1) or 24 mg of HYD/kg BW was administered 0, 2, 4 or 6 times during the treatment period (12 d) with equal time (6 d, 3 d or 2 d) between subsequent injections (Exp. 2). Adrenocorticotropic hormone (ACTH) was injected to provide 0, 5, 10 or 15 IU/kg BW (Exp. 3), or 15 IU ACTH/kg BW was injected 0, 1, 2 or 3 times (Exp. 4). The injection treatment periods were from d 14 to d 26 postpartum. Pancreatic and intestinal amylase activity was maximized by the highest dosage of HYD (24 mg) and ACTH (15 IU) when given at 2- or 4-d intervals, respectively (P less than .10). However, four injections of HYD administered 3 d apart optimized the activity of this enzyme in Exp. 2 (P less than .05). Intestinal sucrase and maltase were unresponsive to ACTH regardless of dosage or injection frequency (P greater than .10). The response of these two enzymes to HYD was inconsistent. Maltase activity was elevated (P less than .10) by the two most frequent injection treatments, and sucrase activity was simultaneously depressed. Lactase activity tended (P less than .15) to be depressed by the highest treatment level in all four experiments. Both dosage and frequency methods of increasing HYD administration resulted in hepatic and pancreatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of digestive carbohydrases and growth to graded doses and administration frequency of hydrocortisone and adrenocorticotropic hormone in nursing piglets. 255 56

Two experiments were conducted that demonstrated that a single injection of hydrocortisone 21-acetate (HYD, 25 mg/kg BW) administered to 6-d-old nursing piglets resulted in a twofold elevation (P less than .02) of pancreatic amylase within 2 d; activity was unaffected by an injection of 15 IU adrenocorticotropic hormone (ACTH)/kg BW (P greater than .20). Intestinal sucrase and maltase activity tended to be elevated (P less than .20) 2 and 4 d postinjection with HYD but returned to normal (uninjected) levels by 14 d of age. The normal decline of intestinal lactase activity was delayed by at least 4 d in response to both hormones (P less than .10). Organ weights were not affected by either hormone. In a separate experiment, postweaning mortality was reduced (12 vs 27%) and growth rate was substantially improved by administration of HYD to piglets 4 and 2 d prior to weaning at 14 d of age. Hydrocortisone resulted in a faster rate of gain the 1st wk postweaning for pigs weaned at 21 or 28 d. Subsequent gain by control and HYD piglets weaned on d 21 was similar, but HYD subsequently impaired growth rate of piglets weaned at 28 d of age. Growth rates of control and ACTH piglets were similar at each postweaning period regardless of weaning age (weaning age [lin.] x week postweaning [quad.] x treatment, P less than .07). This differential treatment response of daily gain may be due in part to effects on feed intake (weaning age [lin.] x week postweaning [lin.] x treatment, P less than .10). We conclude that a single injection of HYD to 6-d-old piglets precociously induces pancreatic amylase and that the sensitivity of piglets to HYD is age-dependent.
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PMID:Temporal changes in carbohydrate digestive capacity and growth rate of piglets in response to glucocorticoid administration and weaning age. 255 57

The excitatory neurotransmitter, L-glutamate (0.5 M, pH 7.4), or the organic acid, acetate (0.5 M, pH 7.4), was microinjected (50 nl over 2 min) directly into the paraventricular nuclei (PVN) of pentobarbital sodium-anesthetized rats while arterial blood pressure and heart rate and plasma adrenocorticotropic hormone (ACTH), vasopressin, and oxytocin were measured. Activation of PVN neurons with L-glutamate led to increases in plasma ACTH, vasopressin, and oxytocin and a profound bradycardia (approximately 80 beats/min) with little change in arterial blood pressure. Microinjection of acetate had no effect on the above variables. The decrease in heart rate was shown to be dependent on the concentration of glutamate injected and the volume of injectate. The bradycardia was mediated through the autonomic nervous system because ganglionic blockade (pentolinium tartrate) eliminated the response; atropine and propranolol severely attenuated the bradycardia. The bradycardia was greatest when L-glutamate was microinjected into the caudal PVN. Injections into the rostral PVN or into nuclei surrounding the PVN led to small or nonsignificant decreases in heart rate. Focal electric stimulation (2-50 microA) of the PVN also led to decreases in heart rate and arterial blood pressure. These data suggest that activation of PVN neurons leads to the release of ACTH, vasopressin, and oxytocin from the pituitary and a bradycardia that is mediated by the autonomic nervous system.
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PMID:Paraventricular stimulation with glutamate elicits bradycardia and pituitary responses. 256 5

The effects of the protein kinase C activator, phorbol myristate acetate (PMA), on cytosolic calcium levels and adrenocorticotropin (ACTH) release from the mouse anterior pituitary tumor cell line, AtT-20, were compared to those induced by the hormone, corticotropin-releasing factor (CRF), a stimulant of cAMP-dependent protein kinase activity. Cytosolic calcium levels were measured using the fluorescence probe Quin 2. PMA induced a time- and concentration-dependent rise in cytosolic calcium levels and ACTH release from AtT-20 cells that was blocked by verapamil and nifedipine, antagonists of voltage-regulated calcium channels, and tetraethylammonium (TEA), a K+ channel antagonist. The inactive phorbol ester, 4-phorbol 12,13-didecanoate, did not alter cytosolic calcium levels or ACTH release. Several minutes after the initial stimulation of calcium influx by PMA, cytosolic calcium levels returned to basal levels despite the continued presence of the phorbol ester. A short pretreatment (2-4 min) of AtT-20 cells with PMA abolished the ability of K+, CRF, and forskolin to raise intracellular calcium levels. These findings indicate that phorbol esters induce a secondary inhibition of calcium influx after an initial stimulation. In contrast to the effects of PMA, CRF induced a sustained rise in cytosolic calcium levels and did not reduce the subsequent stimulation of calcium influx by K+ or PMA. CRF-stimulated calcium influx was blocked by verapamil but not TEA. The ability of CRF to elevate cytosolic calcium levels was mediated by cAMP-dependent protein kinase because the insertion of a synthetic peptide inhibitor of cAMP-dependent protein kinase activity into AtT-20 cells attenuated the ability of CRF and forskolin but not PMA to raise cytosolic calcium levels. The results suggest that activators of protein kinase C and cAMP-dependent protein kinase regulate intracellular calcium levels in AtT-20 cells through different mechanisms.
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PMID:Activators of protein kinase C and cyclic AMP-dependent protein kinase regulate intracellular calcium levels through distinct mechanisms in mouse anterior pituitary tumor cells. 282 94

Different hormones of the hypothalamo-pituitary-adrenal axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) were measured in brain pieces (stalk, median eminence, hypothalamus), hypophyses, adrenals and plasma of 21-day-old rat fetuses from mothers which were given either plain tap water or water containing dexamethasone acetate (10 micrograms/ml) from day 15 to 21 of gestation. Dexamethasone induced drastic reduction of body weight (-66% vs. controls), severe atrophy of the adrenals (-83%) and a sharp drop in their corticosterone content (-74%). Fetal plasma corticosterone levels were below the lower limit of detection of the competitive corticosteroid-binding globulin (CBG) radioassay (less than 0.01 microgram/ml). Both atrophy and severe reduction of the adrenal activity in fetuses from dexamethasone-treated females were in good correlation with a drastic decrease in plasma adrenocorticotropic hormone (ACTH) levels which were below the lower limit of detection of the radioimmunoassay (RIA) used (less than 10 pg/ml) and a significant reduction in pituitary ACTH content (-93%). The low corticostimulating activity of the fetal hypophyses was associated with a drop in both corticotropin-releasing factor (CRF) hypothalamic content (-57%) and concentration (-67%). The effects of dexamethasone on plasma and pituitary ACTH concentrations in 21-day-old fetuses were compared to those, previously reported, of encephalectomy and decapitation performed on day 16 of gestation. The reported data were consistent with the present results, suggesting both pituitary and hypothalamic sites for the in vivo inhibiting action of dexamethasone on the rat hypothalamic-pituitary-adrenal axis in late gestation.
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PMID:Effects of chronic maternal dexamethasone treatment on the hormones of the hypothalamo-pituitary-adrenal axis in the rat fetus. 282 15

Mouse adrenocortical Y-1 tumor cells were examined in a monolayer culture and their steroid secretion was measured. The Y-1 cells constantly released a small amount of steroids in the absence of adrenocorticotropin (ACTH). When synthetic ACTH (tetracosactide acetate) was added to the medium, an increase in the steroid secretion of approximately 5-fold was observed. The Y-1 cells also showed a typical cytoplasmic retraction in response to ACTH. Incubation of the cells with an antimitotic drug, colchicine, prior to ACTH-stimulation resulted in a 30-50% reduction in ACTH-induced steroid secretion. Under the conditions used in these experiments, viable numbers of cell and of total amount of protein per dish were not measurably changed, indicating that the condition was not lethal. Another antimitotic drug, colcemid, caused similar reactions, while lumicolchicine showed no effect. This suggests that the disruption of the microtubular system is the main cause of the inhibition. On the other hand, the ACTH-independent secretion was slightly enhanced by colchicine. The enhancement was also observed in prolonged incubation with colchicine, a condition which caused death in some of the cells.
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PMID:Dual effect of antimitotic drugs on steroid secretion in mouse adrenocortical Y-1 tumor cells. 283 81

In this paper we provide evidence to show that the pathways by which adrenocorticotropic hormone (ACTH) and angiotensin II (AII) stimulate steroidogenesis in bovine fasciculata cells are only partially independent. Both hormones have the same intrinsic activity but a 500-fold higher dose of AII is required to achieve 50% stimulation of steroidogenesis. Whereas ACTH acts by way of cAMP, AII appears to operate through protein kinase C. The phorbol ester, 12-O-tetradecanoylphorbol-13 acetate (TPA), and the calcium ionophore, A23187, each stimulate steroidogenesis and, when added together, act synergistically. To test the relationship between the ACTH and AII pathways, we added the two hormones simultaneously and measured steroid production. When the hormones were present at submaximal concentrations, their effects were additive. At maximal doses, steroid production was 40% above that elicited by either hormone alone. In contrast to the action of AII in the glomerulosa cell where it inhibits ACTH-stimulated cAMP formation, AII causes no inhibition in the fasciculata. Cycloheximide inhibits steroidogenesis stimulated by AII or a mixture of TPA and A23187. Scatchard analysis of the binding of 125I-AII to particulates from adrenal cortical fasciculata indicates the presence of a single class of binding sites (Kd = 0.6 X 10(-8) M). Binding is not inhibited by ACTH. Biotin-containing AII analogs that bind specifically to the particulates have been evaluated as potential tools for avidin-biotin affinity chromatography of the receptor. One of these, [N epsilon-6-(biotinylamido)hexyllys1, Val5] AII, is a promising candidate for receptor isolation.
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PMID:Angiotensin stimulation of adrenal fasciculata cells. 284 22


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