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)

Cytokine-induced release of corticotropin-releasing factor (CRF) from hypothalamic explants in vitro can be inhibited by femtomolar concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH). Because the mechanism of the anticytokine action of alpha-MSH remains unknown, we examined if the peptide inhibits CRF release by interference with various steps in the activation of CRF release. Previous studies have shown that CRF release is induced by activation of phospholipase A2 (PLA2). Therefore, we examined the effect of alpha-MSH on the action of melittin (MEL), a PLA2 activator. After 60 min preincubation in Krebs-Ringer bicarbonate buffer, medial basal hypothalami were incubated for 30 min with Krebs-Ringer bicarbonate buffer or MEL with or without alpha-MSH (10(-11) to 10(-16) M). CRF release into the incubation medium was measured by RIA. As reported previously none of the alpha-MSH concentrations used changed basal CRF release nor did any concentration of alpha-MSH significantly alter CRF release induced by MEL (10 micrograms/ml). Thus, alpha-MSH alters cytokine-induced CRF release at a step unrelated to the activation of PLA2. Because activation of PLA2 requires an increase in intracellular calcium ion (Ca2+) concentrations, we evaluated the effect of alpha-MSH on the release of CRF induced by a high concentration of potassium (56 mM). This concentration of potassium induced a 3.5-fold increase in CRF release that was not affected by alpha-MSH. Protein kinase C (PKC) stimulates CRF release. Consequently, we examined the effect of alpha-MSH on CRF release induced by phorbol myristate acetate (PMA), which in the presence of Ca2+ stimulates PKC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-melanocyte-stimulating hormone inhibits corticotropin-releasing factor release by blocking protein kinase C. 748 28

A peptide inhibiting either corpuscolate or purified PKC has been identified from microsomes of PHA-activated human PBMC but it is not detectable in microsomes of resting PBMC. The peptide was obtained from a microsomal preparation in an oligomeric form that could be transformed into a monomeric form by beta-MSH. The active peptide (IN) was retained on a PC-11 chromatographic column and could be eluted with NaCl. IN is ineffective on PKC-dependent protamine phosphorylation of protamine and on Ca2+ and phospholipid-independent activity generated by mild hydrolysis with trypsin of PKC. Ca2+ binding is permissive for IN activity. IN inhibits particulate PKC in PHA-activated PBMC, but is ineffective after TPA activation. All these data indicate that IN acts at the regulatory domain of PKC.
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PMID:Identification of a novel protein kinase C inhibitor in microsomes from phytohaemagglutinin activated human peripheral blood mononuclear cells. 836 75

Adrenocorticotropic hormone (ACTH) triggers well-defined responses in Y-1 cells. Among them is steroidogenesis stimulation. We have previously shown that phorbol 12-myristate 13-acetate (PMA), an activator of the calcium- and phospholipid-dependent protein kinase (PKC) is able to mimic all the responses triggered by ACTH in these cells, including steroidogenesis stimulation. Short (2 h) treatment with PMA leads to only 20-30% of the maximal steroidogenesis stimulation obtained with ACTH. However, the steroid secretion in the 2 h that follows the short-term (2 h) PMA treatment reaches the same levels as observed with ACTH, i.e., a 12- to 15-fold increase. We also show that this effect is restricted to cells treated with PMA for up to 4 h, while treatment for longer periods of time causes a reduction of the steroid biosynthesis rate, an effect that is not observed in cells treated with ACTH or N6,2'-0-dibutyryladenosine 3',5'-cyclic monophosphate (dcAMP). These results suggest that activation of PKC can elicit the first phase of ACTH steroidogenesis stimulation, but not the second one, which strictly depends on activation of cAMP-dependent protein kinase.
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PMID:Patterns of long-term steroidogenesis stimulation by ACTH and phorbol ester. 873 27

Incubation of rat adrenal glomerulosa cells with low concentrations (up to 50 nM) of the protein kinase (PKC) inhibitor staurosporine (ST) inhibited aldosterone (ALDO) and cyclic AMP (cAMP) production stimulated by adrenocorticotropic hormone (ACTH) and cholera toxin. Only higher concentrations (1.6 microM) of staurosporine inhibited dibutyryl-cAMP- and forskolin-induced stimulation of aldosterone production. cAMP levels were increased only with low concentrations of the PKC inhibitor. This latter increase was avoided by treatment with a maximal concentration of isobutylmethylxanthine (MIX). Our results suggest that: (1) second messengers other than cAMP are involved in ACTH action; (2) staurosporine inhibits different kinases involved in ACTH action in a dose-dependent manner; (3) the protein kinase inhibited by high concentrations of staurosporine appears to be the cAMP-dependent kinase, PKA; and (4) the protein kinase inhibited by low concentrations of staurosporine remains to be identified. This latter species is suggested as being involved in mediating ACTH-induced activation of Gs.
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PMID:Effects of staurosporine on ACTH-mediated stimulation of aldosterone production. 891 88

1. The synthesis and secretion of aldosterone in the adrenal zona glomerulosa in physiologic conditions is controlled by adrenocorticotropin (ACTH), angiotensin II (AII), and extracellular (K+). 2. ACTH effects on aldosterone output are explained by cyclic AMP-(cAMP)- and Ca(2+)-dependent mechanisms. 3. All effects on aldosterone secretion are initiated by an increase in Ca2+ influx through hormone-operated Ca2+ channels and G-protein- and phospholipase C-(PLC) dependent hydrolysis of phosphoinositides leading to the generation of inositol 1,4,5 trisphosphate (IP3) and DAG that induce intracellular Ca2+ release and PKC activation, respectively. 4. ACTH increases DAG formation with marginal or undetectable IP3 generation. The effect of ACTH on DAG levels is discussed. 5. The requirement of external Ca2+ in PLC activation and aldosterone secretion also is discussed.
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PMID:Recent progress in understanding aldosterone secretion. 918 96

We have investigated the signal transduction pathway of the G-protein mu-opioid receptor upstream of phospholipase D (PLD) and protein kinase C-epsilon (PKC-epsilon) activation in postmitotic E6CH chick embryo cortical neurons. The mu-opioid receptor and PLD-PKC-epsilon functional coupling depends on upstream tyrosine kinase activation. We now report that the mu-opioid agonists specifically stimulated tyrosine phosphorylation and activation of the focal adhesion kinase (FAK) in a time-dependent manner. We also demonstrate that met-enkephalin, a mu-opioid agonist in E6CH cultures, significantly increases tyrosine phosphorylation of another Src kinase substrate, the cytoskeletal protein cortactin. Tyrosine phosphorylation of cortactin led to drastic changes in subcellular localization, an estimated 2-fold enrichment in the cytosol. Similarly, opioids stimulated a sustained tyrosine phosphorylation of vinculin, a protein enriched in focal adhesion sites. These data provide novel evidence that opioid receptor intracellular signaling engages the specific activation of tyrosine kinase FAK and regulates the neuronal cytoskeleton during central nervous system morphogenesis.
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PMID:mu-Opioids activate tyrosine kinase focal adhesion kinase and regulate cortical cytoskeleton proteins cortactin and vinculin in chick embryonic neurons. 936 24

Immunocytes from the mollusc Mytilus galloprovincialis express corticotropin-releasing hormone (CRH) receptor subtype (CRH-R1 and CRH-R2)-like mRNAs. Using computer-assisted microscopic image analysis, we have found that exogenous CRH provokes changes in the cellular shape of immunocytes, and that this response is extracellular Ca(2+)-dependent. The various inhibitors of transduction signaling pathways, i.e. suramin sodium, 2', 5'-dideoxyadenosine, neomycin sulfate, calphostin C, H-89, and wortmannin, completely or partially inhibit these changes. The present findings demonstrate that PKA, PKC, and PKB/Akt are involved in CRH-induced cell shape changes in immunocytes, and that the cellular effect of CRH needs the synergistic action of the two second messengers, cAMP and IP(3).
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PMID:Synergistic role of cAMP and IP(3) in corticotropin-releasing hormone-induced cell shape changes in invertebrate immunocytes. 1076 42

At least two hypothalamic peptides, corticotropin releasing hormone (CRH) and vasopressin (VP), are important in regulating adrenocorticotropin (ACTH) release from the anterior pituitary. Both are secreted in a pulsatile manner and stimulate ACTH secretion by interacting with G protein-coupled receptors (GPCRs), namely the type 1 CRH receptor and V1b receptor, respectively. Repeated or prolonged stimulation with either peptide can cause reduced ACTH responsiveness or desensitisation, both in vivo and in vitro. Desensitisation of perifused sheep anterior pituitary cells to VP was found to be rapid and occurred following treatment with 5 nM VP for 5 min. This is within the range of concentrations and durations of VP pulses seen in sheep portal blood during acute stress. In contrast, significant desensitisation of the ACTH response to CRH required pre-treatment for longer than 25 min with a CRH concentration of 1 nM, suggesting that endogenous pulses may not elicit desensitisation. Although rapid GPCR desensitisation involves uncoupling of receptors from their G proteins, commonly mediated by receptor phosphorylation, and internalisation of receptors, desensitisation of neither the CRH nor VP receptor was mediated by PKA or PKC, respectively. Desensitisation of the response to VP was found to be dependent upon receptor internalisation, and resensitisation could be delayed by treatment with a protein phosphatase 2B inhibitor. The rapid kinetics of desensitisation of the ACTH response to VP suggest that this process is important in regulating the response to acute rather than chronic stress. If, as has been suggested, CRH acts in a permissive way to set corticotrope gain, desensitisation to CRH could also be important in long term regulation of ACTH secretion.
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PMID:Acute and chronic regulation of pituitary receptors for vasopressin and corticotropin releasing hormone. 1193 3

Protein kinase C (PKC) has recently emerged as mediator of corticotropin-releasing hormone (CRH) effects. Aim of the present study was to study the effects of CRH on each PKC isoenzyme. As a model we have used the PC12 rat pheochromocytoma cell line, expressing the CRH type 1 receptor (CRHR1). Our data were as follows: (a) CRH-induced rapid phosphorylation of conventional PKCalpha and PKCbeta, accompanied by parallel increase of their concentration within nucleus. (b) CRH suppressed the phosphorylation of novel PKCdelta and PKCtheta;, which remained in the cytosol. (c) CRH-induced transient phosphorylation of atypical PKClambda and had no effect on PKCmu. (d) The effect of CRH on each PKC isoenzyme was blocked by a CRHR1 antagonist. (e) Blockade of conventional PKC phosphorylation inhibited CRH-induced calcium ion mobilization from intracellular stores as well as the CRH-induced apoptosis and Fas ligand production. In conclusion, our findings suggest that CRH via its CRHR1 receptor differentially regulates PKC-isoenzyme phosphorylation, an apparently physiologically relevant effect since blockade of conventional PKC phosphorylation abolished the biological effect of CRH.
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PMID:Corticotropin-releasing hormone activates protein kinase C in an isoenzyme-specific manner. 1564 20

The pars intermedia of the frog (Rana esculenta) pituitary, which is composed of a single population of endocrine cells, the melanotrophs, is a very suitable model to study the mode of action of hypophysiotropic neuropeptides. We have recently characterized neurotensin (NT) in Rana esculenta and found that synthetic frog NT (fNT) stimulates the electrical and secretory activities of melanotrophs. By combining biochemical, pharmacological, microfluorimetric, and electrophysiological approaches, we observed that NT stimulates inositol-trisphosphate production that provokes Ca(2+) release from intracellular stores. The resulting increase in cytosolic Ca(2+) concentration ([Ca(2+)](c)) activates the secretion of alpha-melanocyte-stimulating hormone (alpha-MSH), stimulates Ca(2+)-dependent protein kinase (PKC) activity, and provokes a depolarizing chloride efflux. PKC reduces the amplitude, whereas membrane depolarization increases the frequency of L- and N-type Ca(2+) currents underlain by the action potential discharge. The complex regulatory processes exerted by NT on Ca(2+) signaling likely generate discrete variations in the [Ca(2+)](c) at various distances from secretory vesicles, contributing to the fine-tuning of alpha-MSH secretion.
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PMID:Signal transduction in Rana melanotrope cells: mechanism of action of neurotensin on secretory and electrical activities. 1589 Oct 16


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