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)

Previous work has shown that corticotropin (ACTH) and angiotensin-II (A-II), in addition to their acute steroidogenic effects, exert long-term influences on adrenal cell differentiated function, stimulatory or inhibitory, respectively. Certain nuclear proto-oncogenes have been implicated in the regulation of gene expression in many cell systems. We have investigated the effects of ACTH and A-II on the levels of c-fos, c-jun, and jun-B messenger RNAs (mRNAs), in bovine and ovine (OAC) adrenal fasciculata cells. In both cell types ACTH produced time- (maximum at 1 h) and dose-dependent (ED50 congruent to 10(-12) M) increase in c-fos (2- to 4-fold) and jun-B (10- to 20-fold) mRNA levels but did not affect c-jun. The concentrations required to induce half-maximal mRNA accumulation and cortisol production were similar. A-II also produced a dose-dependent increase in c-fos and jun-B mRNAs but also in c-jun in both cell types, despite the fact that OAC are resistant to the steroidogenic action of the hormone. The stimulatory effects of A-II on c-fos mRNA were higher than those produced by ACTH, whereas the effects on jun-B were similar but ACTH abolished (OAC) or decreased (bovine adrenal fasciculata cells) the stimulatory effects of A-II on c-jun mRNA. The effects of ACTH and A-II on cortisol production and proto-oncogene mRNAs were in part mimicked by 8 Bromo-cAMP and the phorbol ester phorbol-12-myristate-13 acetate plus calcium ionophore A23187, respectively. In the presence of cycloheximide, which blocks the steroidogenic effects of both hormones, proto-oncogene mRNAs were superinduced by both hormones. This result, together with the fact that dexamethasone failed to affect the mRNA levels suggests that the stimulatory effects of ACTH and A-II on proto-oncogene expression were not related to an autocrine/intracrine action of cortisol. Taken together, these findings show that the proto-oncogene mRNAs in normal adrenal cells are regulated by ACTH and A-II, acting through different intracellular pathways. They also demonstrate differential responsiveness of the Jun family to both hormones. Thus, the opposite long-term action of ACTH and A-II on adrenal cell differentiated function could be mediated by its different initial effects on proto-oncogene expression, in particular in the members of the Jun family.
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PMID:Regulation of c-fos, c-jun and jun-B messenger ribonucleic acids by angiotensin-II and corticotropin in ovine and bovine adrenocortical cells. 131 Dec 31

The production of IL-1 and IL-6 by pituitary cells has recently been demonstrated. In this study we investigated the expression of IL-2 and its receptor (IL-2R) by pituitary cells of different species. In Northern blots, a single hybridizing band of 1 kb, identical to that in normal stimulated lymphocytes, was obtained with specific IL-2 probes. In the mouse AT-20 pituitary tumor cell line, IL-2 mRNA expression was detected after stimulation with corticotropin-releasing hormone or phorbol myristate acetate. In human corticotrophic adenoma cells, basal IL-2 mRNA expression as well as IL-2 secretion were further stimulated by phorbol myristate acetate. Both adenoma and AtT-20 cells showed detectable amounts of IL-2R mRNA and by immunofluorescence, IL-2R membrane expression. In addition, dual immunofluorescence studies in rat anterior pituitary cells demonstrated colocalization of IL-2R with ACTH-positive cells and other cell types expressing the receptor. In addition to the action of lymphocyte-produced IL-2, this cytokine may have a paracrine or autocrine regulatory role within the pituitary. It remains to be established whether IL-2 production occurs in the normal pituitary or is intrinsic to the process of tumor development of these cells. IL-2 may be involved in the growth control of pituitary cells.
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PMID:Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures. 133 Nov 77

These studies were undertaken to evaluate the role of protein kinase C (PKC) in the regulation by arginine vasopressin (AVP) of adrenocorticotropin (ACTH) secretion from the ovine anterior pituitary. AVP caused the rapid translocation of PKC from the cytosol to the cell membrane in ovine anterior pituitary cells that was maximal at 5 min. This phenomenon, which is a known concomitant of C-kinase activation, was produced to a greater extent by phorbol 12-myristate 13-acetate (PMA) but not by corticotropin-releasing factor (CRF). To determine whether AVP activated corticotrope PKC, we assessed the ability of three different PKC inhibitors (H-7, sphingosine, and retinal) to modify basal, AVP-, PMA-, and CRF-stimulated ACTH release. In addition to inhibiting the in vitro activity of purified PKC, each compound also caused in vitro inhibition of the protein kinase A (PKA) catalytic subunit, indicating that none could be considered to be a specific inhibitor of PKC and the PKA catalytic subunit. As determined by the mean IC50 values required for the in vitro inhibition of PKC and the PKA catalytic subunit, sphingosine was judged to be the most selective and H-7 the least selective PKC inhibitor. A 4 h exposure to each inhibitor caused a dose-dependent increase in basal ACTH release and attenuation of both AVP- and PMA-stimulated ACTH release. H-7 and retinal, in concentrations that caused a 20-50% inhibition of PKA, also attenuated CRF-stimulated ACTH release; however, this effect was not observed with sphingosine in concentrations that caused only a 10-20% inhibition of PKA. We conclude that: (1) AVP causes the direct activation of PKC in the ovine anterior pituitary and that C kinase activation is important in mediating the effect of AVP on ACTH release; (2) the finding that inhibition of PKC elevates ACTH suggests that basal ACTH secretion is also partly regulated by PKC; (3) since CRF does not cause PKC translocation in ovine anterior pituitary cells, it is unlikely that PKC plays a physiological role in the action of CRF on the corticotrope; (4) the finding that H-7 and retinal attenuate CRF-stimulated ACTH secretion suggests that CRF activates PKA in corticotropes.
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PMID:Evidence that the stimulation by arginine vasopressin of the release of adrenocorticotropin from the ovine anterior pituitary involves the activation of protein kinase C. 133 7

Cells of the immune system produce biologically active adrenocorticotropic hormone (ACTH). Many laboratories, however, have been unable to replicate experiments which demonstrate ACTH in immune cells. Sensitive immunohistochemical staining and digital scanning, confocal microscopy were used to study regulation of ACTH-like immunoreactivity (ACTH-IR) in human mononuclear cells. Cytoplasmic ACTH-IR was induced by corticotrophin releasing factor (CRF)/arginine vasopressin (AVP), and also by protein kinase C (PKC) activation and by the interferon (IFN-alpha beta inducer, Na-polyinosinic-polycytidylic acid (polyIC). Induction of cytoplasmic ACTH-IR was maximal within 6 hr of stimulation with CRF/AVP or phorbol myristate acetate (PMA). Recombinant human interleukin-1 beta (rhIL-1 beta) was also stimulatory, but rhIL-1 alpha had minimal effect. Regulation of ACTH-IR production in immune cells parallels the regulation of ACTH in the anterior pituitary, and ACTH-like material may affect immune responses.
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PMID:Regulation of production of adrenocorticotropin-like proteins in human mononuclear cells. 133 62

Although alpha-MSH increases skin darkening in humans, there are several reports that it fails to have melanogenic effects on human melanocytes in vitro. The purpose of this study was to see whether cultured human melanocytes express MSH receptors. Human melanocytes were grown in the absence of artificial mitogens such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) and cholera toxin (CT) and incubated for 2 h at room temperature with increasing amounts of 125I-labelled Nle4DPhe7-alpha-MSH with and without excess cold peptide. Binding was saturable and specific: Scatchard analysis gave a Kd of 4.9 x 10(-11) M and approximately 700 binding sites/cell. Human keratinocytes and fibroblasts showed no specific binding. The addition of 1 mM dibutyryl cAMP to the culture medium caused a 62% increase in MSH binding to human melanocytes. A smaller increase (25%) was seen with 10(-9) M CT while 25 mM TPA caused a 24% decrease. These results show that human melanocytes in culture express MSH receptors and that this expression can be modulated by mitogens.
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PMID:The expression of functional MSH receptors on cultured human melanocytes. 133 93

The relationship of age-dependent changes in concentrations of various opioid peptides in the brain and pituitary to the development of hypertension was studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats served as controls. Opioids determined were dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three approaches were used: (1) temporal correlations of opioid concentrations with the onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid changes when hypertension development was prevented with antihypertensive drugs and (3) determination of possible opioid peptide changes in another rat model of hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide concentration differences (SHR/WKY) found were as follows. There were much lower DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At 12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE were found in the anterior lobe of the pituitary, but there were higher BE and ME levels found in the neurointermediate lobe (NIL). Prevention of hypertension in SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE and ME changes in the NIL but not in the anterior lobe. There were no brain or pituitary changes in opioid peptide concentrations associated with DOCA-salt hypertension. The results are interpreted as supporting a role for altered concentrations of brain and pituitary opioids in the genesis of SHR hypertension.
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PMID:Age-related changes in opioid peptide concentrations in brain and pituitary of spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison with deoxycorticosterone acetate and salt hypertension. 135 4

Antinociceptive actions and effects of intracerebroventricular (i.c.v.) dynorphin-(1-13) (DYN) on morphine (MOR) analgesia and acute tolerance were studied in male Sprague-Dawley rats. Antinociceptive effect against hind paw pressure was produced by 30 micrograms of DYN, but not by 0.5-10 micrograms. Acetic acid writhing was inhibited dose-dependently by DYN at the doses of 2-30 micrograms, and the order of potency of the anti-writhing effect was beta-endorphin > MOR > DYN >> Met-enkephalin. The anti-writhing effect of DYN that was partially antagonized by naloxone at 10 mg/kg, s.c. in MOR tolerant rats was the same as that in MOR naive rats. The anti-writhing effect of i.c.v.-MOR was increased synergistically by DYN. Continuous s.c. (6 mg/kg/hr) and i.c.v. (7.5 micrograms/rat/hr) infusion of MOR produced antinociception against hind paw pressure, which reached maximum (MAX) and attenuated thereafter during MOR infusion for 6 hr. The attenuation of antinociception was also produced during MOR infusion combined with multiple i.c.v.-injection of DYN. The MAX and area under the antinociceptive curve during MOR infusion was not affected by multiple injection of DYN, i.e., no effect of i.c.v.-DYN on the development of acute MOR tolerance induced by s.c.- and i.c.v.-infusion was observed. In conclusion, the anti-writhing effect of i.c.v.-DYN might not be mediated via mu-receptors, although DYN increased the anti-writhing effect of i.c.v.-MOR synergistically and the development of acute tolerance to MOR (i.c.v., s.c.) was not affected by i.c.v.-DYN.
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PMID:Dynorphin-(1-13): antinociceptive action and its effects on morphine analgesia and acute tolerance. 136 87

The pattern of expression of at least four neuropeptides contained in adrenomedullary chromaffin cells is altered by exposure to the cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha), alone or in combination with stimulation of other second messenger pathways. Vasoactive intestinal polypeptide (VIP) was elevated 2- to 3-fold by 1 nM IL-1 alpha within 48 h of exposure, while neurotensin and substance P synthesis were unaffected, and met-enkephalin levels were decreased 25-35%. Stimulation of VIP and substance P biosynthesis by forskolin was markedly enhanced by IL-1 alpha, while forskolin stimulation of enkephalin and neurotensin biosynthesis was unaffected. IL-1 alpha amplified the effect of phorbol myristate acetate to increase the VIP content of chromaffin cells, but antagonized phorbol ester-induced elevation of neurotensin levels. TNF alpha also demonstrated a neuropeptide-specific pattern of modulation of second-messenger effects on chromaffin cell neuropeptide levels similar to those seen with IL-1 alpha. The neuroendocrine actions of IL-1 alpha described above, unlike IL-1 action in the immune system, do not appear to be mediated through IL-2 as this cytokine did not affect VIP or enkephalin expression in the presence or absence of protein kinase stimulation. Neither IL-1 alpha nor TNF alpha affected the calcium-coupled stimulation of neuropeptide secretion and biosynthesis that occurs in response to cell depolarization in these and other neuroendocrine cells in vitro and in vivo. These data provide a functional demonstration of IL-1 and TNF receptors in chromaffin cell cultures and suggest a physiological role for cytokine production in the adrenal medulla. Since both the magnitude and direction of neuropeptide synthesis modulation by IL-1 alpha and TNF alpha are highly peptide-specific, it appears that these cytokines do not merely augment second messenger pathways that affect neuropeptide synthesis, but potentially regulate the activity of factors controlling the pattern of neuropeptide gene expression in chromaffin cells.
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PMID:Interleukin-1 alpha and tumor necrosis factor-alpha differentially regulate enkephalin, vasoactive intestinal polypeptide, neurotensin, and substance P biosynthesis in chromaffin cells. 137 39

In order to clarify the mechanism of substance P (SP)-induced cortisol secretion from bovine adrenocortical (BAC) cells, protein synthesis at the early stage of SP-stimulation in BAC cells was investigated. Both SP and adrenocorticotropic hormone (ACTH) increased [3H]leucine uptake into BAC cells in a dose-dependent fashion. Although the SP-induced [3H]leucine uptake precedes the cortisol secretion, ACTH was slower in inducing [3H]leucine uptake and cortisol secretion. Protein synthesis inhibitors, actinomycin D and cycloheximide, were potent in inhibiting the SP-induced cortisol secretion. SDS-PAGE analysis, revealed that a 240 kDa protein is newly synthesized in BAC cells in response to SP but not ACTH. It was also indicated that the production of this 240 kDa protein was elicited about 30 min after stimulation by SP. Moreover, A23187 and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also caused a rapid [3H]leucine uptake and production of 240 kDa protein. In contrast, dibutyryl cAMP did not induce the synthesis of this 240 kDa protein. Calmidazolium, a calmodulin inhibitor, effectively inhibited not only [3H]leucine uptake but also 240 kDa protein production due to SP. On the other hand, KT-5720, an inhibitor of protein kinase A, had no effect on [3H]leucine uptake or 240 kDa production. Using the [125I]calmodulin-membrane overlay method, it was found that the 240 kDa protein was a newly synthesized calmodulin binding protein. From the present study, it was concluded that the de novo synthesis of this 240 kDa protein may be intimately related to the cortisol secretion in SP-stimulated BAC cells associated with an activation of the Ca-calmodulin pathway.
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PMID:de novo synthesis of calmodulin binding protein in substance P-induced steroidogenesis in bovine adrenocortical cells. 138

Relatively little is known about the regulation of secretion of hypothalamic beta-endorphin, the potent opioid that is believed to play a variety of physiological roles in brain. Previous work has shown that arginine vasopressin (AVP), which acts in brain primarily via activation of the phosphoinositol (PI) second messenger system, stimulates secretion of hypothalamic beta-endorphin. To test the hypothesis that activators of protein kinase C (PKC), which is activated following PI hydrolysis, stimulates secretion of beta-endorphins from hypothalamus, we studied the separate effects of stimulators of PKC including phorbol ester 12-myristate-13-acetate (PMA) and 1-oleolyl-2-acetyl glycerol (OAG- a diacyl glycerol analogue) on secretion of immunoreactive (IR-) beta-endorphin (measured by RIA) from dissociated fetal rat hypothalamic cell cultures. We also studied AVP and angiotensin II (Ang II), hypothalamic peptides which activate the PI second messenger pathway, and interactions of PMA and forskolin (FSK), an activator of the cyclic AMP/protein kinase A (PKA) pathway. PMA, OAG, AVP, and Ang II stimulated IR-beta-endorphin secretion. The stimulatory effect of both PMA and FSK on IR-beta-endorphin secretion was greater than that of PMA or FSK alone and was essentially additive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase C activators stimulate beta-endorphin secretion from hypothalamic cells. 142 53


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