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)

Thymulin injection into rats (20-150 ng) i.p. caused a significant reduction in both mechanical (paw pressure test) and thermal (hot plate and tail flick tests) nociceptive thresholds. Thymulin injection also doubled IL-1beta level in the liver of these animals. Induced hyperalgesia was reversed completely by alpha-MSH related tripeptide, Lys-D-Pro-Val in low doses, which is known to antagonize IL-1beta and PGE2 induced hyperalgesia, but was only partly reversed by IL-1beta related tripeptide, Lys-D-Pro-Thr at high doses, which is known to antagonize IL-1beta induced hyperalgesia only. We conclude from these results that thymulin causes hyperalgesia and that this effect is at least in part mediated via PGE2 and its effectiveness at low concentration implies a physiological role for this thymic hormone.
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PMID:Hyperalgesia induced by low doses of thymulin injections: possible involvement of prostaglandin E2. 905 72

In domestic ruminants such as the sheep, birth is effected through sequential maturation of the foetal hypothalamic-pituitary-adrenal (HPA) axis, leading to the increased output of cortisol. Factors regulating foetal pituitary adrenocorticotrophin (ACTH) secretion have been delineated, and these include corticotrophin releasing hormone (CRH), arginine vasopressin, prostaglandin (PG) E2 and endogenous opioids. The pre-partum increase in foetal plasma ACTH is associated with a rise in pro-opiomelanocortin (POMC) mRNA in the foetal pars distalis, and with an altered pattern of POMC post-translational processing. Foetal adrenal activation results from an increase in ACTH receptors and enhanced coupling through the Gs protein to adenylate cyclase, and increased expression of key steroidogenic enzymes including P450c17. Cortisol modulates the mechanism by which ACTH activates foetal adrenal function, through specific glucocorticoid receptors (GR) in the foetal adrenal cortex. Although the numbers of GR change with gestation, the relative abundance of GR mRNA does not, pointing to post-translational regulatory mechanisms. Cortisol also stimulates an increase in the concentration of its own high affinity binding protein (corticosteroid binding globulin; CBG) in the foetal circulation, apparently by increasing CBG gene expression in the foetal liver, and by altering the extent of foetal CBG glycosylation in a manner that would be expected to decrease the metabolic clearance of this glycoprotein. Clear evidence for placental CRH and ACTH production is lacking in sheep, but PGE2, produced in increasing amounts by the placenta during late pregnancy, may augment the drive to HPA maturation. Aspects of the maturational pathway of cortisol biosynthesis have been described in other species, including the horse, and some comparison is made with the more detailed information currently available from species such as the sheep.
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PMID:Foetal endocrine maturation. 907 35

Release of beta-endorphin is modulated by physiologic stress and a variety of hormonal and pharmacologic factors. Prostaglandin E2 inhibits release of beta-endorphin and corticotropin from pituitary corticotroph cells, suggesting that suppression of prostaglandin levels should increase beta-endorphin release. This hypothesis was tested by administration of 600 mg ibuprofen before surgical stress in humans in comparison to placebo and methylprednisolone. Plasma samples were analyzed for immunoreactive beta-endorphin with concurrent measurement of pain and apprehension. Levels of immunoreactive beta-endorphin increased during surgery in the placebo group but were significantly greater in the group of patients pretreated with ibuprofen. Methylprednisolone suppressed intraoperative immunoreactive beta-endorphin, compared with both placebo and ibuprofen. Parallel in vivo and in vitro studies indicate that nonsteroidal anti-inflammatory drug potentiation of endorphin release is mediated at the level of the pituitary corticotroph cell. These results show that ibuprofen enhances pituitary release of beta-endorphin by corticotroph cells in response to stress.
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PMID:Ibuprofen elevates immunoreactive beta-endorphin levels in humans during surgical stress. 924 21

The latencies of pain threshold to different subhypnotic doses (12.5, 25 and 50 mg kg-1) of propofol, an anaesthetic, administered intraperitoneally (i.p.) into male mice were measured using a hot plate method. The possible mechanism of pain control by propofol was also investigated through blocking beta-endorphin receptors and measuring serum level of beta-endorphin. Morphine (1.5 mg kg-1; i.p.) was used as a reference of reduction of pain sensation. The results showed that propofol in doses of 25 and 50 mg kg-1 significantly (P < 0.01) increased the latency of pain threshold but a lower dose (12.5 mg kg-1) failed to produce any significant change. This indicates that propofol reduced pain and this effect is dose-dependent. Propofol prevents hyperalgesia produced by prostaglandin PGE2, (0.5 mg kg-1, i.p.; P < 0.01). Pretreatment with naloxone (1.0 mg kg-1, i.p.) abolished significantly (P < 0.01) the antinociceptive action of propofol. Furthermore, serum level of beta-endorphin was increased (P < 0.01) after propofol injection particularly at the peak time of propofol action. The serum level of corticosterone was also increased (P < 0.01) at the time of beta-endorphin release. It was concluded that propofol can control pain and this action may be centrally modulated through the opioid system rather than at the level of the spinal cord.
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PMID:Effect of propofol on perception of pain in mice: mechanisms of action. 977 4

Corticotropin releasing factor (CRF) is a predominant regulator of the neuroendocrine, autonomic and behavioral responses to stress. In addition, numerous studies support autocrine/paracrine roles for this peptide at peripheral sites. CRF and CRF binding sites have been identified in different regions of the central nervous system as well as in the heart, spleen, adrenal and testis, and high levels of CRF were detected in inflamed fibroblasts. However, the precise physiological or pathophysiological role of peripheral CRF cannot yet be discerned. Here we show that CRF, through interaction with specific membrane receptors, blocks the interleukin-1alpha (IL-1alpha)-stimulated prostaglandin (PG) synthesis in fibroblasts. Binding of [125I]-labeled CRF in fibroblasts was saturable and fitted a two sites model. K(D) for the higher-affinity class of receptors was 20+/-2.2 pM, and Bmax 1.95+/-0.22 fmol/mg protein. For the lower-affinity class of receptors K(D) was 160+/-17 nM, and Bmax 2.38+/-0.27 fmol/mg protein. CRF blocked the effect of IL-1alpha on PGE2 synthesis, and this was antagonised by D-PheCRF12-41. In addition, the CRF receptor antagonists alpha helical CRF9-41 and D-PheCRF12-41 at high concentrations inhibited the IL-1alpha-induced PG synthesis similarly to CRF, suggesting partial agonistic action. Taken together, these results suggest a modulatory role of CRF in inflammation.
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PMID:Corticotropin releasing factor modulates interleukin-1-induced prostaglandin synthesis in fibroblasts: receptor binding and effects of antagonists. 980 5

Interleukin-1beta (IL-1beta) and other cytokines produce fever by stimulating prostaglandin E(2) (PGE(2)) synthesis in thermoregulatory regions of the preoptic area and anterior hypothalamus (POA/AH). Prostaglandin E(2) is thought to raise body temperature, at least in part, by stimulating beta-endorphin release from pro-opiomelanocortin neurons that innervate the POA/AH. In this study, we investigated whether glycyl-glutamine (beta-endorphin(30-31)), an inhibitory dipeptide synthesized from beta-endorphin post-translationally, inhibits IL-1beta and PGE(2)-induced hyperthermia. Hyperthermic sites were identified by microinjecting PGE(2) (3 fmol/1 microl) into the medial preoptic area (mPOA) of conscious, unrestrained rats. Interleukin-1beta (1 U) injection into the same PGE(2) responsive thermogenic sites in the mPOA elicited a prolonged rise in colonic temperature (T(c)) (+1.02+/-0.06 degrees C) that persisted for at least 2 h. Glycyl-glutamine (3 nmol) co-injection into the mPOA inhibited IL-1beta thermogenesis completely (T(c)=-0.18+/-0.22 degrees C). Glycyl-glutamine had no effect on body temperature when given alone to normothermic rats. Co-injection of individual amino acids, glycine and glutamine (3 nmol each amino acid), failed to influence IL-1beta-induced thermogenesis, which indicates that Gly-Gln hydrolysis does not explain its inhibitory activity. Glycyl-glutamine (3 nmol) also prevented the rise in body temperature produced by PGE(2) (PGE(2)=0.89+/-0.05 degrees C; PGE(2) plus Gly-Gln=-0.16+/-0.14 degrees C), consistent with evidence that PGE(2) mediates IL-1beta-induced fever. These findings demonstrate that Gly-Gln inhibits the thermogenic response to endogenous pyrogens.
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PMID:Inhibition of interleukin-1beta and prostaglandin E(2) thermogenesis by glycyl-glutamine, a pro-opiomelanocortin-derived peptide. 1125 Dec 8

In the present study, Wistar rats, which received a streptozotocin injection to induce diabetes (STZ-diabetic rats), a model similar to insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes mellitus, were used to investigate the effect of prostaglandin (PG) E2 on plasma glucose. Intravenous injection of PGE2 produced a dose-dependent lowering of plasma glucose level in fasting STZ-diabetic rats after 60 min. In addition to the blockade of this hypoglycemic effect by guanethidine (a noradrenergic nerve terminal-blocking agent), prazosin at a dose effective to block alpha1-adrenoceptors abolished the action of PGE2. An increase of plasma norepinephrine (NE) was also observed in STZ-diabetic rats receiving PGE2 injections. Participation of sympathetic stimulation by PGE2 may thus be speculated. Also, the plasma glucose-lowering effect of PGE2 was also blocked by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid mu-receptor. Injection of PGE2 increased plasma beta-endorphin-like immunoreactivity (BER) in STZ-diabetic rats, and this action was abolished by prazosin. Bilateral adrenalectomy resulted in the loss of this PGE2 effect, and no increase was seen in plasma BER with PGE2 in STZ-diabetic rats. Therefore, beta-endorphin from the adrenal gland appears to be responsible for the lowering of plasma glucose in STZ-diabetic rats by PGE2 through an increase of NE release to activate alpha1-adrenoceptors.
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PMID:Release of beta-endorphin by prostaglandin E2 to lower plasma glucose in streptozotocin-induced diabetic rats. 1150 83

The gastroprotective effect of opioid peptides, prostaglandin E2 and capsaicin against acidified ethanol-induced gastric mucosal damage in young mature rats of different (6-8 and 14-16 weeks) ages has been investigated. It was found that gastric mucosal damage was more severe in 14-16 weeks old rats. The gastroprotective effect of opioid peptides--[D-Ala2, D-Leu5]-enkephalin (DADLE), deltorphin II, [D-Ala2, Phe4, Gly5 -ol]-enkephalin (DAGO) and beta-endorphin--given either intracerebroventricularly (0.6, 3.3, 0.2, and 0.01 nmol/rat, respectively) or subcutaneously (825 and 960 nmol/kg, respectively) was highly reduced in 14-16 weeks old rats. The mucosal protective action of orally administered capsaicin (1600-3200 nmol/kg) and PGE2 (280-560 nmol/kg) was also diminished in 14-16 weeks old animals. Both ACTH and corticosterone plasma levels were significantly higher in 14-16 weeks old rats. These results suggest that the gastric mucosal susceptibility to ethanol and the gastroprotective effect of opioid peptides, capsaicin and PGE2 are age-related.
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PMID:Differences in gastroprotective processes in 6- to 8- and 14- to 16-week-old rats. 1249 1

The effects of interleukin-18 (IL-18), a putative member of the IL-1 family, were investigated on basal and stimulated release of corticotropin-releasing hormone (CRH) and prostanoids from rat hypothalamic explants and glial cells in vitro. We found that IL-18 decreases basal and KCl-stimulated CRH release from the hypothalamus. IL-18 also reduced CRH gene expression after 1- and 3-h incubation. The cytokine did not modify basal PGE2 production by hypothalamic explants but abolished production stimulated by IL-1beta. Similar effects were also observed on cultured glial cells. The present findings show that IL-18 possesses a profile of in vitro neuroendocrine activities opposing to, and even antagonizing, those of IL-1beta.
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PMID:Interleukin-18 displays effects opposite to those of interleukin-1 in the regulation of neuroendocrine stress axis. 1571 Apr 58

Interleukin-1beta (IL-1beta) is involved in hypothalamic regulation of the neuroimmune response by influencing the synthesis and secretion of corticotropin releasing hormone (CRH), vasopressin (VP) and other stress-related mediators. VP secretion from magnocellular (MNC) neurons of the paraventricular nucleus (PVN) of the hypothalamus at the posterior pituitary and/or median eminence contributes to increasing adrenocorticotropin hormone (ACTH) output and ultimately glucocorticoid release, which then contributes to the stress response. In this study, using whole-cell patch clamp recordings from neurons in a slice preparation of the rat PVN, we show that MNC neurons are also influenced by IL-1beta. In response to 1 nM IL-1beta, 62% of MNC neurons tested depolarized (mean depolarization=10.9+/-1.4 mV); effects which were maintained in the presence of a sodium channel blocker, tetrodotoxin (TTX). The effects of IL-1beta on MNC neurons were blocked in the presence of a specific cyclooxygenase (COX)-2 inhibitor, NS-398, indicating a dependence on prostaglandins (PG) in mediating these effects. In response to direct application of 1 muM PGE2, 57% of MNC neurons depolarized, exhibiting a membrane potential change similar to that induced by IL-1beta (mean depolarization=7.8+/-1.1 mV). Voltage clamp experiments examining the effects of PGE2 on the currents evoked by slow voltage ramps revealed activation of a conductance characteristic of a non-selective cationic conductance (NSCC) (voltage-independent, with a reversal potential of -41.8+/-7.6 mV), suggesting that this prostanoid directly modifies cationic currents in MNC neurons. These data provide evidence that IL-1beta depolarizes MNC neurons in the PVN as a result of prostaglandin-mediated activation of a NSCC.
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PMID:Interleukin-1beta depolarizes magnocellular neurons in the paraventricular nucleus of the hypothalamus through prostaglandin-mediated activation of a non selective cationic conductance. 1592 99


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