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)

Neuroendocrine and autonomic responses were assessed in chloralose-anesthetized cats after chemical stimulation of medial brain-stem regions, including those that influence nociceptive input to the medullary or spinal dorsal horn. Microinjections of L-glutamate (0.5 M, 160 nl) were directed at the following rostral and caudal raphe nuclei: the periaqueductal gray (PAG), the dorsal raphe nucleus (DR), the raphe magnus (RM), and the raphe obscurus/raphe pallidus (Ro/Rpa). Activation of DR neurons evoked a significant increase in the adrenal secretion of epinephrine (+2.6 +/- 1.1 ng/min, P less than 0.01) that returned towards prestimulus values by 6 min, whereas microinjections into other raphe nuclei had no consistent effect. Activation of Ro/Rpa neurons evoked an increase in the plasma concentration of adrenocorticotropin (ACTH, +47.9 +/- 12.3 pg/ml, P less than 0.01), whereas microinjections into other raphe nuclei did not affect ACTH. Arterial pressure increased significantly after activation of PAG (+7.5 +/- 2.1 mm Hg, P less than 0.01) or of DR (+4.8 +/- 2.0 mm Hg, P less than 0.05) neurons, whereas heart rate increased significantly (P less than 0.05) after stimulation of cells within the Ro/Rpa. Glutamate microinjections within the RM, a raphe nucleus that exerts a significant descending influence on nociceptive input to the medullary and to the spinal dorsal horns, had no consistent effect on any measured variable. No evidence was seen to suggest that chemical activation of neurons within raphe nuclei inhibited the adrenal secretion of catecholamines or inhibited the release of ACTH. The results indicated that glutamate activation of neurons within different raphe nuclei evoked non-uniform effects on neuroendocrine and autonomic function. Further, these data suggested that the neural substrate underlying the control of the adrenal secretion of catecholamines and of the release of ACTH in response to activation of raphe neurons is likely distinct from that which contributes to the descending influence on nociceptive input to the medullary and spinal dorsal horn.
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PMID:Comparison of the influence of rostral and caudal raphe neurons on the adrenal secretion of catecholamines and on the release of adrenocorticotropin in the cat. 197 77

1. Preliminary, general chemical characteristics of substances in artificial sea water (ASW) washed through stimulated body wall (SBW) and in hemolymph taken from noxiously stimulated animals (SHL) were consistent with those of classical neurotransmitters, amino acids, and small- to medium-sized peptides. 2. 5-Hydroxytryptamine (5HT) and acetylcholine (ACh), unlike SBW and SHL, caused relaxation when perfused into isolated body wall. FMRFamide produced a biphasic response--brief contraction followed by prolonged relaxation. 3. Small cardioactive peptide (SCPB) caused body wall contractions similar to those produced by SBW and SHL, except that SCPB contractions displayed more desensitization and were completely blocked by 30 mM CoCl2. SCPB and SBW contractions were synergistic. 4. Dopamine caused persistent body wall contractions similar to those of SBW and SHL. Dopamine contractions were reduced but not blocked by 30 mM CoCl2. Unlike SBW activity, dopamine activity was reduced by alkalinization. 5. Glutamate and taurine produced strong but usually short-lasting body wall contractions. Adenosine, octopamine, arginine vasotocin, and cholecystokinin (CCK-8) caused weak or variable contractions. Met-enkephalin and somatostatin caused no obvious body wall responses. 6. When superfused over the fully sheathed abdominal ganglion, FMRFamide, met-enkephalin, glutamate, aspartate, and taurine reduced the magnitude of the gill-withdrawal reflex elicited by siphon nerve stimulation. 7. Taken together with earlier results, these data suggest a preliminary framework for trauma signal pathways. It is proposed that stress hormones (perhaps including FMRFamide, SCPs, 5HT, and dopamine) are released into hemolymph from neuroendocrine cells. Effective amounts of active intracellular solutes such as amino acids may also be released by extensive cellular rupture. Various humoral signals produce slow effects that contribute to hemostasis, balling up, increased cardiac output, and reflex suppression.
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PMID:Humoral factors released during trauma of Aplysia body wall. II. Effects of possible mediators. 276 Feb 88

The role of trigeminal nucleus caudalis (Vc) in control of the autonomic and endocrine correlates of nociception was assessed in chloralose-anesthetized cats. Microinjections of the neuroexcitatory agent, L-glutamate (0.5 M), were directed at the marginal layers, at the central magnocellular portion, and at the deep magnocellular portion of Vc. Changes in the plasma concentration of adrenocorticotropin (ACTH), in mean arterial pressure, and in heart rate were examined. Glutamate excitation of neurons within the marginal layers of Vc evoked a significant (+143 +/- 52 pg/ml, P less than 0.01) increase in plasma ACTH during the 10 min postinjection sampling period. Glutamate injections into the deep magnocellular portion of Vc also increased plasma ACTH (+97 +/- 28 pg/ml, P less than 0.05), whereas activation of neurons in the central magnocellular portion of Vc had no consistent effect on plasma ACTH (-25 +/- 29 pg/ml, P greater than 0.10). Arterial pressure increased transiently after glutamate injections into the marginal layers or central magnocellular portion of Vc, whereas injections into the deep magnocellular portion of Vc did not affect arterial pressure. Heart rate increased transiently regardless of the laminar site of injection within Vc. These data indicate that activation of neurons in laminar regions of Vc that process nociceptive information cause an increase in plasma ACTH, whereas activation of neurons in laminae of Vc that process mainly non-nociceptive input have no significant influence on plasma ACTH.
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PMID:Glutamate activation of neurons within trigeminal nucleus caudalis increases adrenocorticotropin in the cat. 290 7

Neonatal treatment of rats with Monosodium Glutamate (MSG) has been demonstrated to destroy cell bodies of neurons in the arcuate nucleus including the brain beta-endorphin (B-END) system. The effects on opiate receptors of the loss of B-END is unknown. Seven to nine month old rats treated with MSG on the first two postnatal days and litter matched untreated control rats were decapitated and their brains dissected into several regions. Opiate receptor assays were carried out with [3H] morphine (mu receptor ligand) and [3H] DADL (delta receptor ligand) for each brain region for both MSG-treated and control rats simultaneously. Scatchard plot analyses showed a selective increase in delta receptors in the thalamus only. No corresponding change in mu receptors in the thalamus was found. The cross-competition IC50 data supported this conclusion, showing a loss in the potency of morphine in displacing [3H] DADL in the thalamus of MSG treated rats.
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PMID:Increase in delta, but not mu, receptors in MSG-treated rats. 629 27

Glutamate plays a role in the central regulation of the hypothalamic-pituitary-adrenal (HPA) and thyroid (HPT) axes. Until the recent discovery of vesicular glutamate transporters (VGLUT1-3), there was no specific tool for the examination of the putative morphological relationship between the glutamatergic and the hypophysiotropic systems. Using antisera against VGLUT2, corticotropin-releasing hormone (CRH), and prothyrotropin-releasing hormone (proTRH) (178-199), we performed double-labeling immunocytochemistry at light and electron microscopic levels in order to study the glutamatergic innervation of the CRH- and TRH-synthesizing neurons in the hypothalamic paraventricular nucleus (PVN). Fine VGLUT2-immunoreactive (IR) axons very densely innervated the parvocellular subdivisions of the PVN. VGLUT2-IR axons established juxtapositions with all parvocellular CRH- and TRH-synthesizing neurons. The innervation was similarly intense in all parvocellular subdivisions of the PVN. At ultrastructural level, VGLUT2-IR terminals frequently established synapses with perikarya and dendrites of the CRH- and proTRH-IR neurons. These findings demonstrate that glutamatergic neurons directly innervate hypophysiotropic CRH and TRH neurons in the PVN and, therefore, support the hypothesis that the glutamate-induced activation of the HPA and HPT axes may be accomplished by a direct action of glutamate on hypophysiotropic CRH and TRH systems.
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PMID:Glutamatergic innervation of corticotropin-releasing hormone- and thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus of the rat. 1578 Oct 46

Glutamate is the dominant excitatory neurotransmitter in a large number of physiological processes including neuroendocrine regulation. Some pharmacological studies have shown that different subtypes of glutamate receptor, such as the N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methy-4-isoxazolepropionic acid (AMPA) receptors, are involved in stress-induced adrenocorticotropin (ACTH) and prolactin secretion. However, the roles of the respective glutamate receptors and the mechanism of ACTH and prolactin secretion during stress via these receptors have not been investigated in detail. In the present study, we evaluated the role of AMPA-type glutamate receptor in ACTH and prolactin regulation under restraint stress in adult male rats. Male rats pretreated with a selective AMPA receptor antagonist, 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX; 50 microg), through a lateral ventricle cannula were stressed by immobilization. Administration of NBQX inhibited ACTH and prolactin secretion in response to restraint stress. However, NBQX had no significant effects on the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis, as measured by the accumulation of 3, 4-dihydroxyphenylalanine (DOPA). In addition, administration of NBQX suppressed stress-induced prolactin secretion in the male rats pretreated with alpha-MT, an inhibitor of dopamine synthesis, and infused with dopamine solution (2.5 microg/200 microl/10 min). These results indicated that the effects of NBQX on prolactin secretion might be mediated by non-dopamine mechanisms. The contents of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the median eminence (ME) of the male rats decreased during restraint stress; however, the fluctuations in CRH and AVP were eliminated by NBQX administration. These results suggest that stress-induced ACTH and prolactin release mediated by neurotransmission via AMPA receptors might be partly attributable to hypophysiotropic regulatory factors in the hypothalamus.
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PMID:Inhibition of stress-induced adrenocorticotropin and prolactin secretion mediating hypophysiotropic factors by antagonist of AMPA type glutamate receptor. 1727 25

Glutamate exerts its effects through binding and activation of two classes of specific receptors: ionotropic (iGluRs) and metabotropic (mGluRs). Group I mGluR includes mGluR1 and mGluR5 subtypes, group II includes mGluR2 and mGluR3 subtypes and group III includes the subtypes mGluR 4, 6, 7 and 8. Glutamate and its receptors are found in all key hypothalamic areas critically involved in reproduction and neuroendocrine function. To date, considerable data support an important role for iGluRs in the control of neuroendocrine function; however, the role of mGluRs as regulators of hypothalamic-pituitary function has not been clearly elucidated. mGluRs could be exerting a fine tune on the release of hypothalamic factors that regulate hormone release such as Substance P, GABA, alpha-MSH and CRH. Group II mGluR exert a direct inhibitory effect on anterior pituitary prolactin and GH secretion. Moreover, some group II mGluR agonists, like LY 354,740 and LY 379,268, can modulate PRL secretion from the anterior pituitary through their actions as dopamine receptor agonists. Evidence suggests a role for group III mGluR subtypes in stress-related behavioral disorders. Several reports indicate that selective ligands for mGluR subtypes have potential for the treatment of a wide variety of neurological and psychiatric disorders, including depression, anxiety disorders, schizophrenia, epilepsy and Alzheimer's disease among others. Since converging lines of evidence suggest a role for mGluRs subtypes in neuroendocrine regulation of hormone secretion, mGluRs neuroendocrine actions must be taken in consideration to insure proper treatment of these diseases. Moreover, discovery of selective agonists provides an opportunity to investigate the physiological role of mGluR subtypes and to directly test the neuroendocrine actions of mGluRs. Finally, mGluRs selective agonists may have an impact in the treatment of conditions involving chronic stress, such as depression and anxiety disorders, since they regulate neuroendocrine stress circuits involving the HPA axis and stress-sensitive hormones such as oxytocin and prolactin. This review aims to provide a survey of our current understanding of the effects of mGluR activation on neuroendocrine function.
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PMID:Role of metabotropic glutamate receptors in the control of neuroendocrine function. 1861 55

Cimicifuga rhizoma has long been used in traditional Korean medicine. In particular, a Cimicifuga heracleifolia extract (CHE) was reported to inhibit the formation of glutamate and the glutamate dehydrogenase activity in cultured rat islet. Glutamate activates melanogenesis by activating tyrosinase. Accordingly, it was hypothesized that a CHE might inhibit the melanogenesis-related signal pathways including the inhibition of microphthalmia-associated transcription factor (MITF)-tyrosinase signaling and/or the activation of extracellular signal-regulated kinase (ERK)-Akt signaling. The results showed that CHE inhibits the cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including MITF, tyrosinase and tyrosinase-related protein (TRP)s in alpha-melanocyte-stimulating hormone-stimulated B16 cells. Moreover, CHE phosphorylates MEK, ERK1/2 and Akt, which are melanogenesis inhibitory proteins. The data suggest that CHE inhibits melanogenesis signaling by both inhibiting the tyrosinase directly and activating the MEK-ERK or Akt signal pathways-mediated suppression of MITF and its downstream signal pathway, including tyrosinase and TRPs. Therefore, C. heracleifolia would be a useful therapeutic agent for treating hyperpigmentation and an effective component in whitening and/or lightening cosmetics.
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PMID:Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells. 1880 55

Stress during childhood and adolescence has implications for the extent of depression and psychotic disorders in maturity. Stressful events lead to the regression of synapses with the loss of synaptic spines and in some cases whole dendrites of pyramidal neurons in the prefrontal cortex, a process that leads to the malfunctioning of neural networks in the neocortex. Such stress often shows concomitant increases in the activity of the hypothalamic-pituitary-adrenal system, with a consequent elevated release of glucocorticoids such as cortisol as well as of corticotropin-releasing hormone (CRH) from neurons. It is very likely that it is these hormones, acting on neuronal and astrocyte glucocorticoid receptors (GRs) and CRH receptors, respectively, that are responsible for the regression of synapses. The mechanism of such regression involves the loss of synaptic spines, the stability of which is under the direct control of the activity of N-methyl-d-aspartate (NMDA) receptors on the spines. Glutamate activates NMDA receptors, which then, through parallel pathways, control the extent in the spine of the cytoskeletal protein F-actin and so spine stability and growth. Both GR and CRH receptors in the spines can modulate NMDA receptors, reducing their activation by glutamate and hence spine stability. In contrast, glucocorticoids, probably acting on nerve terminal and astrocyte GRs, can release glutamate, so promoting NMDA receptor activation. It is suggested that spine stability is under dual control by glucocorticoids and CRH, released during stress to change the stability of synaptic spines, leading to the malfunctioning of cortical neural networks that are involved in depression and psychoses.
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PMID:Stress and anxiety in schizophrenia and depression: glucocorticoids, corticotropin-releasing hormone and synapse regression. 1901 87

Glutamate is the main excitatory neurotransmitter in the central nervous system, and plays an excitatory role in generation of hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. The current study assesses the role of kainate-preferring receptors in glutamatergic excitation of the HPA axis. In situ hybridization and immunohistochemical analyses confirmed the existence of the GluR5 kainate subunit in the paraventricular nucleus of the hypothalamus (PVN). Importantly, GluR5 immunoreactivity was enriched in the external lamina of the median eminence, where it is co-localized with corticotropin releasing hormone (CRH). Intra-PVN infusion of LY382884 increased plasma adrenocorticotropin (ACTH), corticosterone and PVN c-Fos immunoreactivity. Infusions of LY382884 into the median eminence region, on the other hand, reduced restraint induced ACTH release without altering c-Fos expression. Together, these findings provide evidence for glutamate-mediated signaling in control of CRH release at the PVN and median eminence, mediated by way of kainate-preferring receptor complexes.
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PMID:GluR5-mediated glutamate signaling regulates hypothalamo-pituitary-adrenocortical stress responses at the paraventricular nucleus and median eminence. 1945 Sep 32


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