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)

Intravenous injection of nerve growth factor (NGF) into rats produces a dose-dependent (from 0.1 to 5 nmol/kg) increase in circulating concentrations of adrenocorticotropin (ACTH) and corticosterone. We have investigated whether this effect is produced through a direct action on a component of the hypothalamo-pituitary-adrenocortical axis. NGF (50 and 500 nM), added to the incubation medium of in vitro isolated pituitary segments or dispersed adrenal cells, did not modify either basal and stimulated release of biologically active or immunoreactive ACTH or release of corticosterone, respectively. The presence of NGF in the incubation medium of in vitro isolated hypothalami produced a dose-dependent (from 150 to 600 nM) increase of both release and content of some material with corticotropin-releasing bioactivity. The nature of this corticotropin-releasing bioactivity was determined directly by radioimmunoassays. Results have indicated that NGF induced an increase of both release and content of hypothalamic arginine-vasopressin (AVP), while no changes were observed in the release and content of hypothalamic corticotropin-releasing hormone (CRH). These results suggest that adrenocortical stimulation by NGF in vivo could be mediated by the release of hypothalamic AVP rather than CRH. The finding that in vivo NGF stimulatory effect was not abolished by the specific CRH antagonist alpha-helical CRH(9-41), while it was accompanied by an increase in circulating AVP levels, supports this interpretation. However, the fact that the hypothalamus is stimulated in vitro by NGF concentrations higher than those expected to reach this structure after systemic injection of active doses raises the possibility that other brain areas such as the hippocampus participate in NGF-induced adrenocortical activation.
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PMID:Hypothalamic involvement in the activation of the pituitary-adrenocortical axis by nerve growth factor. 826 66

Peptides that regulate the growth of tissues, whether in a positive or negative manner, are termed growth factors. The melanocortins, neurotrophic sequences that correspond to peptide fragments contained within ACTH-(1-13), beneficially affect neural growth during development and regeneration. Analogues of ACTH-(4-9) (Org 2766) and ACTH-(4-10) (BIM 22015) are capable of sustaining neurite outgrowth from cultured dorsal root ganglion and spinal cord cells in the absence of nerve growth factor. The development of sexually dimorphic behavior in both male and female rats is influenced by perinatal administration of ACTH. This change appears to be correlated with changes in the growth and metabolism of developing serotonergic and dopaminergic systems in the hypothalamic nuclei associated with male and female sexual behavior. Similar melanotropic influences are found in the developing neuromuscular system. Neuromuscular development is accelerated by perinatal administration of melanocortins, provoking both nerve and muscle to attain early maturation. However, the responding tissue varies pivotally with age: early in gestation, embryonic muscle is acutely sensitive to peptide exposure; but once innervation has occurred, only the developing nerve reacts to melanocortin treatment. Melanocortins have little if any effect on the normal, adult neuromuscular system. Following peripheral nerve injury or pathology, melanotropins once again become effective growth factors, accelerating and enhancing nerve regeneration and muscle reinnervation. Electrophysiological, morphological, biochemical, and functional tests all indicate that ACTH-(4-10), Org 2766, BIM 22015, and alpha-MSH improve various facets of nerve regeneration, the degree to which the specific parameter is improved being dependent on the peptide fragment, its dosage, and pattern of administration. BIM 22015, while less effective as a neurotrophic factor, has potent myotrophic effects that the other peptides lack. Org 2766 may provide some protective action to the injured CNS as demonstrated by tests of cognitive function following brain lesions, although evaluation of recovery is sometimes enigmatic. Recovery from destruction of the nigrostriatal system is more easily measured through tests of motor function and open field behavior, both of which support a protective role for Org 2766. Compensatory mechanisms, including the presence of increased tyrosine hydroxylase and greater density of dopaminergic fibers, may be involved. Melanocortins are effective growth factors in sciatic nerve regeneration in neonatal rats. Both alpha-MSH and ACTH-(4-10) favor the formation of morphologically normal end plates despite the trauma following nerve crush at postnatal day 2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Melanotropins as growth factors. 839 Jan 55

Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic neurons that are activated in response to stress, yet their relationship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocorticotropic hormone (ACTH) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complementary to intronic sequences of genes encoding ACTH secretagogues in parvocellular neurosecretory neurons of the paraventricular nucleus, we found these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120 min). To identify candidate mechanisms regulating peptide expression, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth factor I-B (NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response element-binding protein (CREB), using antisera specific to its transcriptionally active, phosphorylated form (pCREB). After ether exposure, c-fos and NGFI-B mRNA induction were maximal at 30--60 min, whereas Fos protein peaked at 60--120 min. Brn-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induced in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time courses that are compatible with control mechanisms involving phosphorylation events and de novo protein synthesis, respectively.
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PMID:Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons. 861 92

Infants with cryptogenic infantile spasms seem to differ from those with symptomatic spasms in having a higher cerebrospinal fluid corticotropin content, different levels of corticotropin release after exogenous vasopressin, higher serum levels of progesterone, higher dehydroepiandrosterone: androstenedione ratio (during corticotropin therapy), a higher cerebrospinal fluid gamma-aminobutyric acid content, and higher cerebrospinal fluid nerve growth factor concentrations. It remains to be seen whether the biochemical differences between the two groups are specific or only happen to correlate with the early brain damage. However, these differences would explain many pathophysiologic features of infantile spasms.
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PMID:How do cryptogenic and symptomatic infantile spasms differ? Review of biochemical studies in Finnish patients. 887 6

Injury to the sciatic nerve leads to the transganglionic degeneration of sensory axons and to the induction of neurotrophins and p75 nerve growth factor receptor synthesis by the denervated Schwann cells. Sciatic nerve axotomy caused a marked loss of substance P and of met-enkephalin in the lumbar cord. Substance P immunostaining and pre-proenkephalin mRNA expression were reduced in the dorsal horn layers I and II ipsilaterally to the lesion. Treating rats with low doses (0.25 mg/kg) of heparin or COS 8, a natural glycosaminoglycan mixture with low anticoagulant activity, the peptide loss was prevented and the content increased of about 50% above control values. The effects of COS 8 treatment were also evident on Schwann cells. COS 8 augmented the increase of nerve growth factor, brain-derived neurotrophic factor, and NT-3 mRNA expression in the distal stump of the axotomized sciatic nerve. Therefore, it can be concluded that glycosaminoglycans neuroprotective effects on lesioned sensory axons might have been mediated by the dramatic promotion of neurotrophin synthesis. Although the in vitro studies (Lesma et al.: J Neurosci Res, 1996) suggested also a likely direct effect as extracellular matrix components that is not mediated by trophic factors.
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PMID:Glycosaminoglycans in nerve injury: II. Effects on transganglionic degeneration and on the expression of neurotrophic factors. 895 69

RESP18 (regulated endocrine-specific protein of 18 KD) is an endoplasmic reticulum (ER) protein that was identified by coordinate dopaminergic regulation with pro-opiomelanocortin in the rat neurointermediate pituitary. Many attributes of RESP18 suggest an important function in neuroendocrine cells. Several neuropeptides, growth factors, and enzymes involved in biosynthesis of classical chemical neurotransmitters, have been identified in germ cells, Sertoli cells, and spermatozoa. In this study, screening of reproductive tissues revealed high levels of RESP18 protein and mRNA in the testes but not in ovaries or epididymis. The testes and sperm expressed 18-KD RESP18 and a unique 19-KD isoform. To better understand RESP18 expression in the testes, we have examined the stages of the cycle of the seminiferous epithelium by immunohistochemistry and Western blot analyses. Immunohistochemical analysis showed that RESP18 protein was expressed exclusively in spermatocytes and maturing spermatids. RESP18 protein was expressed at high levels in Step 1-8 round spermatids, in which the PC4 prohormone convertase, nerve growth factor, and proenkephalin are also expressed. Western blots, Northern blots, and indirect immunofluorescence staining demonstrated RESP18 expression in sperm.
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PMID:Stage-specific expression of RESP18 in the testes. 898 41

Cocaethylene is an active cocaine metabolite formed by hepatic carboxylesterases in the presence of alcohol. The effects of cocaethylene on the hypothalamic-pituitary-adrenal (HPA) axis were investigated in vivo using adrenocorticotropic hormone (ACTH) and corticosterone secretion as indices of peripheral stimulation. To ascertain the central effects of cocaethylene on discrete neurons of the paraventricular nucleus (PVN) of the hypothalamus, a specific cRNA probe was used to follow changes in the transcriptional activation of nerve growth factor I-B (NGFI-B), a member of the family of immediate-early genes. Intravenous (i.v.) injection of cocaethylene (16 mumol/kg) to rats produced a marked but transient increase in plasma levels of ACTH and corticosterone within 10 min of drug exposure. Secretion of these hormones was accompanied by elevated levels of NGFI-B mRNA detected 30 min after i.v. or intraperitoneal (i.p., 60 mumol/kg) cocaethylene administration. The transcriptional stimulation of this immediate-early gene within parvocellular secretory neurons was relatively brief in duration, returning to basal levels by 180 min after drug exposure. As expected both routes of cocaethylene administration produced an increase in locomotor activity compared to saline-vehicle rats, with no differences between i.v. or i.p. routes with respect to duration of behavioral activation. Taken together, these findings indicate that cocaethylene has neuroendocrine properties on its own, targeting a critical region of the brain that regulates stressful events in the body. This, combined with other neurochemical properties, points to the possibility of cocaethylene augmenting the effects of a drug-dependent state.
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PMID:Cocaethylene stimulates the secretion of ACTH and corticosterone and the transcriptional activation of hypothalamic NGFI-B. 903 37

In this paper we report a time-course study of development of experimental allergic encephalomyelitis in Lewis rats, by monitoring neuroendocrine regulation of the hypothalamus-pituitary-adrenal axis through corticotropin-releasing hormone mRNA expression, inflammatory cellular infiltrate, macrophagic and neuronal nitric oxide synthase, nerve growth factor (NGF), and NGF p75 and trkA receptors in the brain and spinal cord. We analyzed animals during 20 days after immunization, a time interval that corresponds to the acute immunological phase. We have described a severe, early fall of corticotropin-releasing hormone mRNA expression, which could account for the decreased response of the hypothalamus-pituitary-adrenal axis to inflammatory stress. During this period, an increase of neuronal nitric oxide synthase was observed in the cerebral cortex and spinal cord, and macrophagic nitric oxide synthase positive cells were found in the inflammatory cellular infiltrate, which was abundant in perivascular and submeningeal areas 20 days after immunization. Concomitantly, we found a dramatic up-regulation of NGF receptors on the wall of blood vessels and adjacent neurons in perivascular areas. NGF content also had increased in some brain areas, such as the thalamus, while it had decreased in others, like the spinal cord and medulla oblongata, at time points in which the most serious cellular infiltrate was found.
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PMID:Time-course changes of nerve growth factor, corticotropin-releasing hormone, and nitric oxide synthase isoforms and their possible role in the development of inflammatory response in experimental allergic encephalomyelitis. 909

1. The modulator effects of a series of neurotransmitters and related substances were tested on responses to adenosine 5'-triphosphate (ATP) at a recombinant P2x2 receptor expressed in defolliculated Xenopus oocytes. 2. Nicotine, 5'-hydroxytryptamine (5-HT), noradrenaline, adenosine, bradykinin and histamine (all 100 microM) potentiated the responses to ATP (3 microM). an effect found due to acidification of the bathing solution by these drugs. 3. Arachidonic acid, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP) (all 100 microM) and nerve growth factor (NGF; 50 ng ml-1) potentiated the responses to ATP (3 microM) through a largely or wholly pH-independent effect. 4. Small acidic and alkaline shifts, as little as 0.03 pH-units, enhanced or diminished the responses to ATP, respectively. A linear relationship existed between the degree of potentiation of the ATP-induced responses caused by nicotine, 5-HT, noradrenaline, adenosine, bradykinin and histamine and the potentiation of these responses induced by the addition of acid to the superfusate. 5. Since P2x receptors on sensory neurones include P2x2 subunits, the attendant acidosis and ATP-release associated with tissue injury may play a role in sensitizing sensory nerve fibres.
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PMID:Potentiation of ATP-responses at a recombinant P2x2 receptor by neurotransmitters and related substances. 911 13

Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons. J. Neurophysiol. 78: 2363-2371, 1997. Patch-clamp and calcium imaging techniques were used to assess the acute effects of the neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF), on the responses of cultured and acutely isolated hippocampal and cultured striatal neurons to the glutamate receptor agonist N-methyl--aspartic acid (NMDA). The effects of BDNF on NMDA-activated currents were examined in greater detail. Currents evoked by NMDA, and the accompanying changes in intracellular calcium, were enhanced by low concentrations of the neurotrophins (1-20 ng/ml). The potentiation by the neurotrophins was rapid in onset and offset (<1 s). The neurotrophins also reduced desensitization of these currents in most cells. The enhancement of NMDA-activated currents by BDNF was observed using both perforated and whole cell patch recording techniques and could be demonstrated in outside-out patches. Furthermore, its effects were not attenuated by pretreatment with the protein kinase inhibitors genistein or 1-(5-isoquinolynesulfony)2-methylpiperazine (H7). Therefore, the actions of BDNF do not appear to be mediated by phosphorylation. Similar enhancements were observed with NT-3 and NT-4 and with NGF despite the fact that hippocampal neurons lack TrkA receptors. All together this evidence suggests that the enhancement of NMDA-evoked currents is unlikely to be mediated through the activation of growth factor receptors. Modulation of NMDA responses by BDNF was dependent on the concentration of extracellular glycine. The most pronounced potentiation by BDNF was observed at low concentrations, whereas no potentiation was observed in saturating concentrations of glycine, suggesting that BDNF may have increased the affinity of the NMDA receptor for glycine. However, the competitive glycine-site antagonist 7-chloro-kynurenic acid blocked the enhancement by BDNF without shifting the dose-inhibition relationship for this antagonist, and Mg2+ consistently depressed the potentiation of NMDA-evoked currents by BDNF, indicating that BDNF does not alter glycine affinity. BDNF also reversibly increased the probability of opening of NMDA channels recorded from outside-out patches taken from cultured hippocampal neurons. Other unrelated peptides including dynorphin and somatostatin also caused a glycine-dependent enhancement of NMDA currents and depressed the currents in saturating concentrations of glycine. In contrast, a shortened analogue dynorphin (6-17), which lacks N-terminus glycine residues, and another peptide met-enkephalin were without effects on NMDA currents recorded in low concentrations of glycine. Our results suggest that neurotrophins and other peptides can serve as glycine-like ligands for the NMDA receptor.
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PMID:Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons. 935 88


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