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)

The possible involvement of alpha-MSH-like peptides in the regenerative response of peripheral nerves was investigated with a competitive antagonist of alpha-MSH, the synthetic hexapeptide [D-Trp7,Ala8,D-Phe10)alpha-MSH(6-11)-amide. Subcutaneous administration of the alpha-MSH antagonist during the first 10 days following sciatic nerve crush significantly decreased functional recovery as measured by the foot flick withdrawal test and the walking pattern analysis. Hypophysectomy delayed both the initial sprouting response and the outgrowth rate after major caudal nerve crush. When hypophysectomized rats were treated with the alpha-MSH antagonist, a further delay in initial sprouting was observed, whereas the outgrowth rate of nerve fibers was not affected. These results suggest that 1) endogenous alpha-MSH-like peptides stimulate nerve outgrowth following peripheral nerve injury and 2) alpha-MSH-like peptides derived from a source other than the pituitary may contribute to the physiological stimulus leading to sprouting.
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PMID:Pharmacological evidence for the involvement of endogenous alpha-MSH-like peptides in peripheral nerve regeneration. 778 62

Melanocortins accelerate functional recovery after nerve crush and enhance neurite outgrowth in vitro. To get more insight in the mechanism of action of melanocortins, we studied the effects of two neurotrophic peptides: alpha-melanocyte-stimulating hormone (alpha MSH) and an adrenocorticotropin4-9 analogue Org 2766 on second messengers in cultures of spinal cord (SC), dorsal root ganglion (DRG) and Schwann cells. alpha MSH (10 microM) enhanced the forskolin-induced cAMP production in SC- (45%) and in DRG-cells (35%). Org 2766 (1 microM) induced an increase in cAMP only in SC-cells (39%). The peptides did not affect the cAMP levels in Schwann cells. Neither peptide evoked significant changes in the intracellular free calcium concentration ([Ca2+]i) in batch-measurements of all cell types, however, Ca(2+)-imaging revealed an infrequent occurrence of large [Ca2+]i-elevations in individual SC-neurons. The results indicate that SC- and DRG-cells are targets for both peptides, while Schwann cells are not or exploit different pathways. We observed for alpha MSH that cAMP production always coincides with outgrowth stimulation, whereas for Org 2766 cAMP production and outgrowth stimulation appear not causally related. These differences in second messenger stimulation could be explained by receptor heterogeneity. We suggest that alpha MSH and Org 2766 act through different receptors, each with its own signalling pathways.
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PMID:The role of calcium and cAMP in the mechanism of action of two melanocortins: alpha MSH and the ACTH4-9 analogue Org 2766. 785 62

Short peptide sequences of ACTH 1-39 (the ACTH 4-9 analog Org 2766, ACTH 4-10 and its analog BIM 22015, and ACTH 1-13 [alpha-MSH]), which do not stimulate the adrenal cortex, have profound effects on the developing and regenerating neuromuscular system, in neonatal and in adult rats. Both development and regeneration are accelerated, as indicated by improved morphological, electrophysiological, behavioral and biochemical parameters. Regeneration in the central nervous system is problematic but the ACTH peptides may provide protection for CNS neurons, enhance denervation sensitivity or permit compensatory processes which facilitate functional recovery. Neuronal cells in culture respond to ACTH peptides by greater neurite outgrowth, and in some cell types, by increased B-50 expression. In all cases, susceptibility to ACTH peptide treatment varies with cell type, age, the specific peptide administered, its dosage and pattern of administration. External stress and the gender of the animal are additional factors that interact with the neurotrophic actions of the melanocortins.
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PMID:Non-corticotropic ACTH peptides modulate nerve development and regeneration. 827 76

Melanocortins, peptides related to alpha-melanocortin-stimulating hormone (alpha MSH) and adrenocorticotropic hormone (ACTH), are known to improve axonal regeneration following peripheral nerve injury and stimulate neurite outgrowth from central nervous system (CNS) neurons both in vitro and in vivo. The neurite outgrowth promoting capacity of alpha MSH has prompted us to investigate the effects of intrathecal application of alpha MSH on functional and electrophysiological recovery in a well-characterized model of spinal cord contusion injury. Different doses of alpha MSH were applied via osmotic minipumps into the cisterna magna for 10 days, thereby delivering the peptide directly into the CNS. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie, and Bresnahan locomotor rating scale, and the thoracolumbar height test. At the end of the study, electrophysiological analysis of rubrospinal motor evoked potentials as performed. Our data showed that application of 3.75 micrograms/kg/h alpha MSH resulted in a marked functional recovery, accompanied by a decrease in the latency of the rMEP. This study demonstrates that intrathecal application of alpha MSH results in functional recovery after spinal cord contusion injury. These findings may initiate new treatment strategies and/or the use of melanocortins in human spinal cord injury.
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PMID:Functional recovery after central infusion of alpha-melanocyte-stimulating hormone in rats with spinal cord contusion injury. 1022 18

Our objective was to determine the least invasive surgical procedure; to do this we compared postoperative pain, duration of ileus, and level of neurohormonal stress response after laparoscopic cholecystectomy (LC) and open cholecystectomy (OC). Postoperative recovery of patients was faster after LC than OC but comparison of the neurohormonal stress response after laparoscopic and open surgical procedures revealed conflicting results. Forty-one consecutive patients with noncomplicated gallstones were randomized for LC (N = 25) and OC (N = 16). The stress level was evaluated in patients before surgery by the Hamilton anxiety scale. Postoperative pain was assessed by a visual analogic scale (VAS) pain score and by the amount of analgesic drugs (propacetamol) administered, while the duration of ileus was determined by the delay between surgery and the time to first passage of flatus as well by the colonic transit time (CTT) measured by radiopaque markers. Plasma concentrations of anti-diuretic hormone (ADH), adrenocorticotropic hormone (ACTH), beta-endorphin (BE), neurotensin (NT), and aldosterone (Ald) were measured before and during surgery as well as 2 and 5 hr after the surgery (D0) and on the day following surgery (D1). Urinary cortisol (uCOR) and urinary catecholamine metabolites were assessed before surgery, during D0, and on D1. Patient characteristics, the duration of surgery, and the doses of anesthetic drugs were not different in LC and OC. In LC patients the VAS pain score and the doses of postoperative antalgics were lower (P < 0.05), the time to first passage of flatus was shorter (P < 0.001), and the CTT tended to be shorter (54 +/- 12 hr vs 81 +/- 17) compared to OC patients. Patients who required the highest doses of postoperative antalgics had the longest delay to first passage of flatus (P < 0.01). During surgery, all neurohormonal parameters increased compared to the preoperative period (P < 0.05), and only plasma NT concentrations were lower during LC than OC (P < 0.05). During the postoperative period, ACTH, BE, Aid, catecholamines, and uCOR concentrations were lower in LC than in OC (P < 0.05). Concentrations of hormonal parameters were higher when the duration of surgery increased (P < 0.05). A greater need for propacetamol to relieve pain was associated with a greater increase in BE, ACTH, and urinary catecholamine levels (P < 0.05-P < 0.005). When the time to first passage of flatus was delayed, levels of BE, ACTH, and catecholamines and NT concentrations were increased (P < 0.05-P < 0.005). In conclusion, LC is less invasive because this surgical procedure induces a shorter neurohormonal stress response than OC, even if the peroperative response is not different. Postoperative pain levels and the duration of ileus are associated with BE, ACTH, and catecholamine levels and NT concentrations, suggesting the importance of hormones in postoperative functional recovery.
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PMID:Operative stress response is reduced after laparoscopic compared to open cholecystectomy: the relationship with postoperative pain and ileus. 1105 8

Housing rats in an enriched environment improves functional outcome after ischemic stroke, this may reflect neuronal plasticity in brain regions outside the lesion. Which components of the enriched environment that are of greatest importance for recovery after brain ischemia is uncertain. We have previously found that enriched environment and social interaction alone both improve functional recovery after focal cerebral ischemia, compared with isolated housing with voluntary wheel-running. In this study, the aim was to separate components of the enriched environment and investigate the effects on some potential mediators of improved functional recovery; such as the inducible transcription factors nerve growth factor-induced gene A (NGFI-A) and NGFI-B, and the glucocorticoid and serotonin systems. After permanent middle cerebral artery occlusion, rats were divided into four groups: individually housed with no equipment (deprived group), individually housed with free access to a running wheel (running group), housed together in a large cage with no equipment (social group) or in a large cage furnished with exchangeable bars, chains and other objects (enriched group). mRNA expression of inducible transcription factors, serotonin and glucocorticoid receptors was determined with in situ hybridisation 1 month after cerebral ischemia. Rats housed in enriched or social environments showed significantly higher mRNA expression of NGFI-A and NGFI-B in cortical regions outside the lesion and in the CA1 (cornu ammonis region of the hippocampus), compared with isolated rats with or without a running wheel. NGFI-A and NGFI-B mRNA expression in cortex and in CA1 was significantly correlated to functional outcome. 5-Hydroxytryptamine receptor 1A (5-HT(1A)) mRNA expression and binding, as well as 5-HT(2A) receptor mRNA expression were decreased in the hippocampus (CA4 region) of the running wheel rats. Mineralocorticoid receptor gene expression was increased in the dentate gyrus amongst wheel-running rats. No group differences were found in plasma corticosterone levels or mRNA levels of glucocorticoid receptor, corticotropin-releasing hormone, 5-HT(2C) or c-fos. In conclusion, we have found that social interaction is a major component of the enriched environment regarding the effects on NGFI-A and NGFI-B expression. These transcription factors may be important mediators of improved functional recovery after brain infarctions, induced by environmental enrichment.
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PMID:Effects of postischemic environment on transcription factor and serotonin receptor expression after permanent focal cortical ischemia in rats. 1280 85

Ischemic stroke is one of the main causes of death and disability. We investigated whether melanocortin peptides, which have protective effects in severe hypoxic conditions, also produce neuroprotection in a gerbil model of ischemic stroke. A 10-min period of global cerebral ischemia, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory that was associated with activation of inflammatory and apoptotic pathways, including severe DNA damage and delayed neuronal death, in the hippocampus. Treatment with nanomolar doses of the melanocortin analog [Nle4, D-Phe7] alpha-MSH [which activates the melanocortin receptor subtypes (MC) mainly expressed in central nervous system, namely MC3 and MC4] modulated the inflammatory and apoptotic cascades and reduced hippocampus injuries even when delayed up to 9 h after ischemia, with consequent dose-dependent improvement in subsequent functional recovery. The selective MC3 receptor agonist gamma2-MSH had no protective effects. Pharmacological blockade of MC4 receptors prevented the neuroprotective effects of [Nle4, D-Phe7] alpha-MSH and worsened some ischemia outcomes. Together, our findings suggest that MC4 receptor-stimulating melanocortins might provide potential to develop a class of drugs with a broad treatment window for a novel approach to neuroprotection in ischemic stroke.
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PMID:Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia. 1648 82

Melanocortin peptides have been shown to produce neuroprotection in experimental ischemic stroke. The aim of the present investigation was to identify the therapeutic treatment window of melanocortins, and to determine whether these neuropeptides chronically protect against damage consequent to brain ischemia. A 10-min period of global cerebral ischemia in gerbils, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory (Morris test: four sessions from 4 to 67 days after the ischemic episode), associated with neuronal death in the hippocampus. Treatment with a nanomolar dose (340 microg/kg i.p., every 12 h for 11 days) of the melanocortin analog [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH), starting 3-18 h after the ischemic episode, reduced hippocampal damage with improvement in subsequent functional recovery. The protective effect was long-lasting (67 days, at least) with all schedules of NDP-alpha-MSH treatment; however, in the latest treated (18 h) gerbils, some spatial memory deficits were detected. Pharmacological blockade of melanocortin MC(4) receptors prevented the protective effects of NDP-alpha-MSH. Our findings indicate that, in conditions of brain ischemia, melanocortins can provide strong and long-lasting protection with a broad therapeutic treatment window, and with involvement of melanocortin MC(4) receptors, 18 h being the approximately time-limit for stroke late treatment to be effective.
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PMID:Broad therapeutic treatment window of [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone for long-lasting protection against ischemic stroke, in Mongolian gerbils. 1664

In gerbils subjected to transient global cerebral ischemia, melanocortin peptides produce long-lasting protection with a broad time window, and through the activation of central nervous system melanocortin MC(4) receptors. Here we aimed to investigate whether melanocortins are neuroprotective also in a rat model of focal cerebral ischemia induced by intrastriatal microinjection of endothelin-1. The vasoconstrictor agent endothelin-1 caused a significant impairment in spatial learning and memory, as well as in sensory-motor orientation and limb use, associated with severe striatal morphological damage including intense neuronal death and an almost complete myelin degradation. Treatment of ischemic rats with a nanomolar dose (340 microg/kg/day i.p. for 11 days, beginning 3 h or 9 h after endothelin-1 microinjection) of the melanocortin analog [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) significantly reduced striatal damage, and improved subsequent functional recovery, with all scheduled NDP-alpha-MSH treatments. Pharmacological blockade of melanocortin MC(4) receptors prevented the protective effect of NDP-alpha-MSH. Our findings give evidence that melanocortins are neuroprotective, with a broad time window, also in a severe model of focal cerebral ischemia, and suggest that melanocortin MC(4) receptor agonists could produce neuroprotection in different experimental models of ischemic stroke.
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PMID:Neuroprotection in focal cerebral ischemia owing to delayed treatment with melanocortins. 1758 64

Melanocortin peptides afford strong neuroprotection and improve functional recovery in experimental ischemic stroke; they also have established neurotrophic actions. The expression of the immediate early gene Zif268 is dependent on synaptic activity and is involved in injury repair and memory formation. Here, we investigated the role of Zif268 in learning and memory recovery after delayed treatment of ischemic stroke with the melanocortin analog [Nle(4), D-Phe(7)]alpha-MSH (NDP-alpha-MSH). A 10-min period of global cerebral ischemia was induced by occluding both common carotid arteries in gerbils. Treatment with a nanomolar dose of NDP-alpha-MSH (every 12h for 11 days) was performed starting 3h or 9h after stroke induction; where indicated, gerbils were pretreated with the melanocortin MC(4) receptor antagonist HS024. Animals were subjected to the Morris water-maze test (four sessions from 4 to 50 days after the ischemic episode). Fifty days after stroke, histological damage and Zif268 expression were investigated in the hippocampus. Treatment with NDP-alpha-MSH significantly reduced hippocampal damage, including neuronal death, and improved learning and memory recovery. This protective effect was long-lasting (50 days, at least) and associated with Zif268 overexpression, with both schedules of NDP-alpha-MSH treatment. Pharmacological blockade of MC(4) receptors prevented these effects. Our data indicate that MC(4) receptor-mediated actions of melanocortins could trigger repair mechanisms able to improve neuronal functionality and synaptic plasticity, and to promote long-lasting functional recovery from ischemic stroke with Zif268 gene involvement.
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PMID:Functional recovery after delayed treatment of ischemic stroke with melanocortins is associated with overexpression of the activity-dependent gene Zif268. 1934 27


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