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 effects of the mu-opioid receptor agonists buprenorphine and morphine on immune and neuroendocrine functions through acute action in the rat mesencephalon periaqueductal gray (PAG) were evaluated. Buprenorphine is an analgesic recently approved for the treatment of drug dependency. In this study, it was shown that injection of an equianalgesic dose of buprenorphine (related to morphine) into the ventral-caudal PAG did not alter splenic NK cell, T cell, and macrophage functions, whereas morphine significantly (p<0.001) suppressed splenic NK cell cytotoxic activity (14-50% reduction), splenic and thymic T cell proliferation to concanavalin A (Con A, 43-76% reduction), antiTCR (T cell receptor) (85% reduction) and IL-2 (36-48% reduction), and macrophage functions including nitric oxide (36-41% reduction) and TNF-alpha production (26%), and phagocytosis of Candida albicans (39%). In addition, buprenorphine was associated with significant (p<0.0001) reductions in adrenocorticotropic hormone (ACTH) and corticosterone (CSO) plasma levels, without altering norepinephrine (NE) and serotonin splenic dialysate levels. In contrast, morphine significantly (p<0.0001) increased glucocorticoid and catecholamine levels in plasma and spleen dialysates, respectively. These results indicated that buprenorphine did not activate either the hypothalamic-pituitary-adrenal (HPA) axis with glucocorticoid release, or the sympathetic nerve (SNS) activity with bioamine production, and was not associated with immunosuppression. The lack of effects of buprenorphine on neuroendocrine systems may be related to its partial agonist properties, the absence of effects on immune system function, and may be associated with the reduction in craving observed in addictive disorders.
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PMID:Differential effects of buprenorphine and morphine on immune and neuroendocrine functions following acute administration in the rat mesencephalon periaqueductal gray. 1093 12

The release of adrenocorticotropin (ACTH) from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH). Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC) in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.
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PMID:Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection. 1100 12

Reflexive erection initiated by recruitment of penile afferents, involves both autonomic and somatic efferents. The reflex is mediated at the spinal cord level, modulated by supraspinal influences, and may use several transmitters. Dopamine, acetylcholine, nitric oxide, and peptides, such as oxytocin and ACTH/alpha-MSH, seem to have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. Peripherally, the balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa, and determines the functional state of the penis. Noradrenaline contracts both corpus cavernosum and penile vessels via stimulation of alpha1-adrenoceptors. The role of endothelins in the control of penile smooth muscle tone is presently unclear. Neurogenic nitric oxide (NO) is considered the most important factor for relaxation of penile vessels and corpus cavernosum. The role of other mediators, released from nerves or endothelium has not been definitely established. International Journal of Impotence Research (2000) 12, Suppl 4, S26-S33.
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PMID:Neurotransmitters: central and peripheral mechanisms. 1103 83

Nitric oxide (NO) as well as beta-endorphin are involved in the neuroendocrine control of gonadotropin-releasing hormone (GnRH) secretion. Recently, morphological and microdialysis experiments have suggested that beta-endorphin may exert an inhibitory influence on NO release in the preoptic area of rat hypothalamus. The present study determines if the mu opioid receptor mRNA is expressed in neuronal NO synthase (nNOS)-immunopositive neurons and if this expression varies among the regions of the basal forebrain being examined. We found, through the use of immunohistochemical and in situ hybridization techniques, that the mu opioid receptor mRNA is expressed in a representative subpopulation of nNOS-immunoreactive neurons in the rat preoptic area. Interestingly, the mu opioid receptor mRNA/nNOS-immunoreactive coexpression is predominant in the rostral and median preoptic area, containing most of GnRH cell bodies. These results strongly suggest that beta-endorphin, via an action through mu opioid receptors, may directly participate in the regulation of NO production in the preoptic area. Our results strengthen the hypothesis that beta-endorphin may participate in GnRH neuronal modulation at the cell body level by regulating NO release from the interneurons of the preoptic area that express nNOS.
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PMID:Mu opioid receptor mRNA expression in neuronal nitric oxide synthase-immunopositive preoptic area neurons. 1103 28

Subjects with human immunodeficiency virus type 1 (HIV-1) infection display increased activity of the hypothalamo-pituitary-adrenal (HPA) axis, which may play a role in both HIV-related neurodegenerative processes and disease progression. It has been speculated that the HIV coat protein gp120 may be responsible for these changes, and previous experimental evidence in both transgenic and nontransgenic mice supports this view. We speculated that one of the effects of gp120 in the CNS is to act within the hypothalamus to affect both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), the principal regulators of HPA axis. We therefore administered i.p. gp120 (100 ng/rat) or vehicle to male Wistar rats and then detected Fos protein (an index of neuronal activation), CRH, and AVP immunoreactivity in the cellular compartments of the hypothalamic paraventricular nucleus (PVN). In addition, we tested the direct effect of various concentrations of gp120 on the release of CRH and AVP from rat hypothalamic explants maintained in vitro. Any modulation of gp120 effects by nitric oxide (NO) pathways was also sought by coadministering i.p. to rats or adding to the hypothalamic preparations the NO synthase inhibitor N(G)-methyl-l-arginine (l-NMMA). Gp120 induced the expression of Fos protein in both the parvo- and the magnocellular PVN, which was significantly attenuated by l-NMMA 10(-6) nM/L (P < 0.001 vs gp120 alone). Double immunochemistry showed costaining for Fos protein and CRH or AVP in the PVN following gp120; the number of double-labeled CRH and AVP cells for Fos protein was markedly reduced (P < 0.001) by coadministration of l-NMMA 10(-6) nM/L. In the in vitro studies, addition of gp120 to the hypothalamic explants in the dose range of 10 pM-1 nM resulted in a clear stimulation of both CRH and AVP release (P < 0.05-0.001 compared to control); in the presence of l-NMMA at 10-fold higher concentrations the stimulatory effect of gp120 on the release of both peptides was completely lost. It would therefore appear that gp120 activates CRH and AVP-producing neurons in the hypothalamic PVN and stimulates the release of both peptides in vitro via NO-dependent mechanisms. These findings, in line with previous evidence, further suggest that the increased activity of the HPA axis associated with HIV infection may be of central origin, due to the effects of gp120 on hypothalamic CRH and AVP release.
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PMID:Stimulating effect of HIV-1 coat protein gp120 on corticotropin-releasing hormone and arginine vasopressin in the rat hypothalamus: involvement of nitric oxide. 1108 2

It is becoming increasingly clear that nitric oxide (NO), an active free radical formed during the conversion of arginine to citrulline by the enzyme NO synthase (NOS), is a critical neurotransmitter and biological mediator of the neuroendocrine axis. Current evidence suggests that NO modulates the activity of both the hypothalamic-pituitary-gonadal axis and the hypothalamic-pituitary-adrenal axis. Supporting this hypothesis is the finding that the highest expression of neuronal NOS in the brain is found within the hypothalamus in areas where the cell bodies of the neurons from the different neuroendocrine systems are located. In this regard, the influence of neuronal NO on the regulation of the neuroendocrine neural cell body activity has been well-documented whereas little is known about NO signaling that directly modulates neurohormonal release into the pituitary portal vessels from the neuroendocrine terminals within the median eminence, the common termination field of the adenohypophysiotropic systems. Studies in rat suggest that NO is an important factor controlling both gonadotropin-releasing hormone (GnRH) and corticotropin-releasing hormone (CRH) release at the median eminence. The recent use of amperometric NO detection from median eminence fragments coupled to the use of selective NOS inhibitors demonstrated that a major source of NO at the median eminence might be endothelial in origin rather than neuronal. The present article reviews the recent progress in identifying the origin and the role of the NO produced at the median eminence in the control of neurohormonal release. We also discuss the potential implications of the putative involvement of the median eminence endothelial cells in a neurovascular regulatory process for hypothalamic neurohormonal signaling.
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PMID:Median eminence nitric oxide signaling. 1108 85

The gas nitric oxide is a messenger in brain signaling. In the hypothalamo-hypophyseal system nitric oxide is involved in the control of the expression and/or release of peptide hormones (corticotropin-releasing hormone, gonadotropin-releasing hormone, vasopressin and oxytocin). Nitric oxide synthase (NOS), the enzyme generating nitric oxide, is abundantly present in the magnocellular nuclei of the rat hypothalamus. Its localization in the human hypothalamus is less well studied. Hence, we investigated the anatomical distribution of neuronal nitric oxide synthase in the human supraoptic nucleus by use of immunohistochemical and enzyme histochemical techniques. The immunohistochemical localization of NOS was studied in 31 matched human hypothalami (13 control cases, eight depressed patients and ten schizophrenics). NADPH-diaphorase studies were carried out on seven additional hypothalami (three normal brains, four schizophrenics). Apparent inter-individual differences exist with regard to the occurrence of the enzyme in supraoptic neurons. In a majority of cases no immunostaining or histochemical reaction for the enzyme was observed. In seven cases (three controls, two schizophrenics, two depressives) a population of nitrergic nerve cells was seen in the dorsomedial part of the nucleus. This group of cells also stained for NADPH-diaphorase. Also, there were a few NOS-immunopositive neurons scattered throughout the nucleus. Additionally, thin NADPH-diaphorase positive fibers were observed to cross the nucleus. Our data show that, unlike the rat, the human supraoptic nucleus contains only a small number of nitrergic neurons. No correlation was found between the expression of the enzyme in supraoptic neurons and the psychiatric status of the patients.
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PMID:Low and infrequent expression of nitric oxide synthase/NADPH-diaphorase in neurons of the human supraoptic nucleus: a histochemical study. 1111 9

The cross-talk between the endocrine and the immune systems mediated by a wide array of hormones, cytokines, and neuromodulators is heightened during disease, stress, and presumably, during pregnancy. Adrenocorticotropin (ACTH) and nitric oxide (NO) are two immunomodulators that are also produced from lymphocytes and contribute to the immunomodulation. Thus, we investigated whether the heightened bidirectional communication between the immune and the endocrine systems observed during pregnancy is reflected in production of ACTH and NO from peripheral bovine lymphocytes and if any temporal correlation exists between them. Adrenocorticotropin was analyzed using a sandwich immunoradiometric assay, and nitrite and nitrate (a measure of NO) were estimated in supernatants of cultured peripheral blood lymphocytes (PBLs) using a colorimetric assay based on the Griess reaction. A significantly high secretion of ACTH and NO was noticed from PBLs in all stages of pregnancy compared to that in cyclic and cystic cows. Increased secretory capacity was noticed as early as 7 days after conception, which reached as much as 600% that of nonpregnant animals between Days 90-120 of gestation. Adrenocorticotropin and NO decline 1 mo before the expected time of parturition. Unlike those from cyclic animals, PBLs from pregnant cows were refractory to stimulation by PHA-M (Phytohemagglutinin) and corticotropin-releasing hormone. A strong correlation was observed between ACTH and NO secretion from PBLs in pregnant, in cyclic, and in cystic cows. To our knowledge, this is the first evidence elucidating the induction of ACTH and NO from PBLs during pregnancy, and it implies a new role for ACTH and NO secreted from PBLs in recognition and, probably, maintenance of pregnancy.
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PMID:Pregnancy stimulates secretion of adrenocorticotropin and nitric oxide from peripheral bovine lymphocytes. 1113 80

The gaseous radical nitric oxide (NO) is catalyzed by conversion of L-arginine to L-citrulline by one cytokine inducible form (iNOS), which becomes active only within hours after the inducing event, and by two constitutively expressed forms, endothelial (eNOS) and neuronal (nNOS), which are regulated by the cytosolic concentration of free Ca2+. Brain nNOS is physiologically present in discrete populations of neurons, which are all excited by glutamate via the ionotropic N-methyl-D-aspartate (NMDA) receptor, which controls a Ca2+ channel. After its diffusion into the extraneuronal space, NO may activate in neurons, which as a rule do not stain for NOS, soluble guanylyl cyclase and formation of cGMP as an intracellular messenger. Beyond that, NO is important as a feedback regulator of glutamatergic excitation. NO as a nitrosylating agent enhances disulfide bonding of vicinal sulfhydryl (thiol) groups of the redox modulatory site of the NMDA receptor complex and thereby down-regulates its Ca2+ channel activity. Histochemical studies have revealed the presence of a large number of NOS containing neurons in the magnocellular and parvocellular subdivisions of hypothalamic nuclei. Numerous studies conform to the view that NO participates in the control of many different neurosecretory processes, especially of the corticotropin-releasing hormone (CRH) neurosecretory system. The redox-modulatory site of the NMDA receptor appears, therefore, as a critical structure in the control of the hypothalamic-pituitary-adrenocortical (HPA) axis. Moreover, glucocorticoids augment neuronal excitotoxicity by increasing the expression of glutamate receptors and inhibition of glutamate reuptake. In attempting to explain the many conflicting results obtained in studies with NO, it may be worthwhile to consider that the actual redox-environment of distinct loci of the brain may determine the final function of NO, acting either as a transmitter or neuromodulator or, in the worst case, causing neurodestruction. It seems likely that any kind of stress by altering the ratio of reduced vs oxidized thiols within the central nervous system influences neuronal excitability, with NO working either as an amplifier or as a feedback regulator of neuronal excitation or inhibition, which may alter acutely or chronically, among others, the homeostasis of a given neurosecretory system.
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PMID:Role of nitric oxide in the control of the hypothalamic-pituitary-adrenocortical axis. 1115 2

The pro-opiomelanocortin-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) mediates broad anti-inflammatory and immunomodulatory effects, which include inhibition of the production and release of proinflammatory cytokines and nitric oxide (NO) from macrophages. We investigated the effects of alpha-MSH, alpha-MSH(1-10), and alpha-MSH(11-13) on NO production and nuclear factor-kappaB (NF-kappaB) translocation in RAW 264.7 macrophages. After stimulation of the cells with bacterial lipopolysaccharide/interferon-gamma (LPS/IFN-gamma), all three peptides inhibited NO production with an order of potency alpha-MSH > or = alpha-MSH(11-13) > alpha-MSH(1-10). All three MSH peptides inhibited NF-kappaB nuclear translocation with the maximal effect of alpha-MSH and alpha-MSH(11-13) being seen in the range 1 nM-1 microM, and that of alpha-MSH(1-10) at 1 microM. By use of (125)I-(Nle(4),D-Phe(7))alpha-MSH(NDP-MSH) radioligand binding, MC(1) receptor-binding sites were demonstrated on RAW 264.7 cells. alpha-MSH and alpha-MSH(1-10) competed with the (125)I-NDP-MSH binding at these MC(1) receptor-binding sites, but alpha-MSH(11-13) even in concentrations up to 1 mM did not. Moreover, alpha-MSH and alpha-MSH(1-10) caused powerful stimulation of cyclic 3',5'-adenosine monophosphate (cAMP) in the RAW 264.7 cell, whereas alpha-MSH(11-13) was ineffective. Forskolin stimulated cAMP and inhibited NO production to the same extent as alpha-MSH and alpha-MSH(1-10), but did not modify the translocation of NF-kappaB. Whereas the protein kinase A inhibitor H89 did not modify the effect of alpha-MSH on NF-kappaB translocation, H89 caused a partial inhibition of the inhibitory effect of alpha-MSH, alpha-MSH(1-10), alpha-MSH(11-13), and forskolin on NO production. In addition alpha-MSH, alpha-MSH(1-10), alpha-MSH(11-13), and forskolin also inhibited the activity of an NF-kappaB-dependent luciferase reporter and these effects were partially counteracted by H89. We suggest that melanocortin peptides act via dual mechanisms of action: one cAMP-independent and causing inhibition of NF-kappaB translocation and the other dependent on MC(1) receptor/cAMP activation.
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PMID:Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. 1123 5


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