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)

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 gut of silver eels (Anguilla anguilla L.) was investigated in order to describe both the cholinergic and adrenergic intramural innervations, and the localization of possible accessory neuromediators. Histochemical reactions for the demonstration of nicotinamide adenine dinucleotide phosphate, reduced form-(NADPH-)diaphorase and acetylcholinesterase (AChEase) were performed, as well as the immunohistochemical testing of tyrosine hydroxylase, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP), bombesin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), somatostatin, cholecystokinin-octapeptide (CCK-8), serotonin, cholineacetyl transferase. The results evidenced a different pattern in comparison with other vertebrates, namely mammals, and with other fish. Both NADPH-diaphorase and AChEase activities were histochemically detected all along the gut in the myenteric plexus, the inner musculature and the propria-submucosa. Tyrosine hydroxylase immunoreactivity was observed in the intestinal tract only, both in the myenteric plexus and in the inner musculature. Several neuropeptides (metenkephalin, CGRP, bombesin, substance P, VIP, NPY, somatostatin) were, in addition, detected in the intramural innervation; some of them also in epithelial cells of the diffuse endocrine system (met-enkephalin, substance P, NPY, somatostatin). Serotonin was only present in endocrine cells. Tyrosine hydroxylase immunoreactivity was present in localizations similar to those of NADPH-diaphorase-reactivity, and in the same nerve bundles in which substance P- and CGRP-like-immunoreactivities were detectable in the intestinal tract. In addition, NADPH-diaphorase-reactive neurons showed an anatomical relationship with AChEase-reactive nerve terminals, and a similar relationship existed between the latter and substance P-like immunoreactivity.
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PMID:Neurotransmitters and putative neuromodulators in the gut of Anguilla anguilla (L.). Localizations in the enteric nervous and endocrine systems. 1109 1

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

During infection, bacterial and viral products, such as bacterial lipopolysaccharide (LPS), cause the release of cytokines from immune cells. These cytokines can reach the brain by several routes. Furthermore, cytokines, such as interleukin-1 (IL-1), are induced in neurons within the brain by systemic injection of LPS. These cytokines determine the pattern of hypothalamic-pituitary secretion that characterizes infection. IL-2, by stimulation of cholinergic neurons, activates neural nitric oxide synthase (nNOS). The nitric oxide (NO) released diffuses into corticotropin-releasing hormone (CRH)-secreting neurons and releases CRH. IL-2 also acts in the pituitary to stimulate adrenocorticotropic hormone (ACTH) secretion. On the other hand, IL-1 alpha blocks the NO-induced release of luteinizing hormone-releasing hormone (LHRH) from LHRH neurons, thereby blocking pulsatile LH but not follicle-stimulating hormone (FSH) release and also inhibiting sex behavior that is induced by LHRH. IL-1 alpha and granulocyte macrophage colony-stimulating factor (GMCSF) block the response of the LHRH terminals to NO. The mechanism of action of GMCSF to inhibit LHRH release is as follows. It acts on its receptors on gamma-aminobutyric acid (GABA)ergic neurons to stimulate GABA release. GABA acts on GABAa receptors on the LHRH neuronal terminal to block NOergic stimulation of LHRH release. IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH-releasing hormone (GHRH) release, which is mediated by NO, and stimulating somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of PRL release is also mediated by intrahypothlamic action of NO, which inhibits release of the PRL-inhibiting hormone dopamine. The actions of NO are brought about by its combined activation of guanylate cyclase-liberating cyclic guanosine monophosphate (cGMP) and activation of cyclooxygenase (COX) and lipoxygenase (LOX) with liberation of prostaglandin E2 and leukotrienes, respectively. Thus, NO plays a key role in inducing the changes in release of hypothalamic peptides induced in infection by cytokines. Cytokines, such as IL-1 beta, also act in the anterior pituitary gland, at least in part via induction of inducible NOS. The NO produced inhibits release of ACTH. The adipocyte hormone leptin, a member of the cytokine family, has largely opposite actions to those of the proinflammatory cytokines, stimulating the release of FSHRF and LHRH from the hypothalamus and FSH and LH from the pituitary directly by NO.
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PMID:The mechanism of action of cytokines to control the release of hypothalamic and pituitary hormones in infection. 1126 67

Administration of adrenocorticotropic hormone (ACTH) leads to the development of hypertension. Because glucocorticoids can affect the nitric oxide system at several sites, the present study tested the hypothesis that nitric oxide synthase (NOS) expression may be altered in ACTH-induced and corticosterone-induced hypertension in the rat. This was addressed by measuring Nos1, Nos2, and Nos3 mRNA in the kidney, adrenal gland, heart, and hypothalamus of 16 ACTH-treated and 16 vehicle-treated rats as well as in 10 corticosterone-treated and 10 control rats. In addition, in situ hybridization and immunohistochemistry were used to confirm changes by detection of Nos in RNA and NOS protein in tissues. Systolic blood pressure of ACTH and corticosterone rats was elevated (165+/-6 and 162+/-11 mm Hg; P<0.001 versus control). Each Nos isoform mRNA was measured by reverse transcriptase-polymerase chain reaction technique. In ACTH rats, mRNA for Nos2 was reduced in renal cortex by 58+/-5% and in medulla by 68+/-7%; for Nos3, mRNA reductions of 59+/-6% and 51+/-11% were seen (P<0.001 after Hochberg correction for multiple comparisons). In corticosterone rats, Nos2 mRNA decreased in cortex by 68+/-5% and in medulla by 62+/-6%; Nos3 mRNA by 50+/-8% in cortex, and Nos1 by 29+/-7% in medulla (all P<0.001 after Hochberg correction). Reductions seen in kidney were supported by in situ hybridization and immunohistochemistry. Apart from a 62+/-2% decrease in Nos2 mRNA in adrenal of ACTH rats (corrected P<0.05), no significant changes were seen in the other nonrenal tissues for any isoform. In conclusion, we have shown for the first time that the physiological components of glucocorticoid action (ACTH and corticosterone) when given chronically in vivo reduce Nos2 and Nos3 expression in the kidney. Such changes are consistent with a role in hypertension for ACTH and corticosterone.
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PMID:Decreased renal expression of nitric oxide synthase isoforms in adrenocorticotropin-induced and corticosterone-induced hypertension. 1130 19

In the dorsal horn of the spinal cord, activation of small fibre nociceptive afferents leads to the release of nitric oxide and enkephalins by interneurons. In this work we encountered unexpected relationships among local spinal cord dorsal horn blood flow, specific forms of afferent input, nitric oxide and intrinsic opioids. Selective rises in rat lumbar dorsal cord blood flow using laser Doppler flowmetry and microelectrode hydrogen clearance polarography were generated by ipsilateral, 'nociceptive' low (3 Hz) frequency stimulation of sciatic afferents. Inhibitors of nitric oxide synthase (NOS) prevented rises in flow during stimulation without influencing baseline flow. Ipsilateral hindpaw intradermal injection of capsaicin, a nociceptive activator, also generated large rises in flow sensitive to NOS inhibition. During NOS blockade or morphine administration there were unexpected acute declines in the dorsal cord blood flow strictly confined to low frequency stimulation epochs. This acute vasoconstrictive effect was prevented by administration of an opioid receptor antagonist. Using immunohistochemistry, terminals apparently innervating dorsal spinal cord blood vessels were labelled with antibodies against neuronal NOS and met-enkephalin. We conclude that local nitric oxide and opioids, probably from interneurons, have competitive actions on dorsal horn microvessels once interneurons are activated during a nociceptive barrage. Collateral innervation of blood vessels may explain this property.
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PMID:Evidence that nitric oxide- and opioid-containing interneurons innervate vessels in the dorsal horn of the spinal cord of rats. 1131 43

The effect of different opioid peptides on acidified ethanol- and indomethacin-induced gastric mucosal lesions was studied following intracerebroventricular (i.c.v.) administration. It was found that both the selective delta opioid receptor agonists--deltorphin II, [D-Ala(2), D-Leu(5)]-enkephalin (DADLE), [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE)-, mu-opioid receptor agonist--[D-Ala(2), Phe(4), GlyT-ol]-enkephalin (DAGO)--as well as beta-endorphin inhibited the mucosal damage induced by both ethanol and indomethacin in pmolar dose range. In contrast, the gastric acid secretion was not influenced by DADLE in the dose of 16 nmol/rat and only a slight reduction (40%) was induced by DAGO in the dose of 1.9 nmol/rat. The protective effect was abolished in both ulcer models by bilateral cervical vagotomy. N(G)-nitro-L-arginine, an inhibitor of NO synthase, reduced the protective action in ethanol-induced, but not in indomethacin-induced gastric damage. The results suggest that activation of supraspinal delta and mu-opioid receptors resulted in inhibition of gastric mucosal lesions elicited by ethanol or indomethacin. The gastroprotective action is independent from the effect of opioids on acid secretion. Vagal nerve is involved in conveying the central action to the periphery. The mechanism of the gastroprotective effect of opioids is different in ethanol- and indomethacin-ulcer models: prostaglandins and nitric oxide are likely to be involved in the protective action of opioid peptides in ethanol-, but not in the indomethacin-ulcer model.
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PMID:Activation of central opioid receptors may induce gastric mucosal defence in the rat. 1159 36

The biological actions of corticotropin-releasing hormone (CRH) in the human myometrium during pregnancy and labor are unknown. We hypothesized that CRH may modulate the nitric oxide system, and influence myometrial relaxation/contractility. Incubation of myometrial cells with CRH, but not urocortin II or urocortin III, for 8-16 h significantly induced mRNA and protein expression of endothelial and brain but not inducible nitric oxide synthase (NOS) isoforms. This action resulted in increased activity of soluble guanylate cyclase (GC(s)), demonstrated by the enhanced cGMP-producing capacity of the NO donor, sodium nitroprusside. CRH also caused acute activation of the membrane-bound GC, shown by increased basal or atrial natriuretic peptide (ANP)-stimulated cGMP production. These effects appeared to be mediated via the R1 receptors because the CRH receptor antagonists, astressin and antalarmin but not anti-sauvagine 30, could block them. The acute effects of CRH were significantly reduced by inhibition of protein kinase A (PKA) activity, suggesting it is partially PKA dependent. Activation of protein kinase C (PKC) resulted in significant inhibition of both ANP-and CRH-stimulated cGMP production, suggesting a direct effect of PKC on membrane-bound GC. In conclusion, CRH appears to have a dual effect on myometrial NOS/GC pathway, a short term effect predominantly mediated by PKA, and a long-term effect increasing constitutive NOS expression, mediated by a PKA-independent mechanism. This mechanism could potentially be active during human pregnancy, and, because cGMP stimulates myometrial relaxation, these findings further suggest that during pregnancy CRH primarily activates intracellular signals that contribute to the maintenance of myometrial quiescence.
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PMID:Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells. 1185 58

Stress and depression have a significant impact on modern society. Even though their symptomatology is well characterized, little is known about the molecular mechanisms underlying these disturbing disorders. While the role of neurotransmitters such as serotonin, norepinephrine (NE), dopamine (DA), corticotropin-releasing hormone (CRH), and arginine vasopressin (AVP) has been extensively studied, new evidence suggests a role for the unique neurotransmitter nitric oxide (NO). This highly diffusible and reactive molecule is synthesized by at least three enzyme subtypes of NO synthase (NOS). The commonly known neuronal NOS subtype is localized in areas of the brain related to stress and depression. The limbic-hypothalamic-pituitary-adrenal (LHPA) axis is the core of this system. These interrelated pathways have in common the production, and negative feedback, of glucocorticoids. Within these areas, NO is suggested to play a role in modulating the release of other neurotransmitters, acting as a cellular communicator in plasticity and development, and/or acting as a vasodilator in regulation of blood flow. This article summarizes some of the recent advances in the understanding of the role of NO in stress and depression.
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PMID:Nitric oxide, stress, and depression. 1239 68

Since D-aspartate stimulates prolactin and LH release, our objective was to determine whether D-aspartate modifies the release of hypothalamic and posterior pituitary factors involved in the control of their secretion and whether its effects on these tissues are exerted through NMDA receptors and mediated by nitric oxide. In the hypothalamus, D-aspartate stimulated luteinizing hormone-releasing hormone (LHRH), alpha-melanocyte-stimulating hormone (alpha-MSH) and GABA release and inhibited dopamine release through interaction with NMDA receptors. It increased nitric oxide synthase (NOS) activity, and its effects on LHRH and hypothalamic GABA release were blunted when NOS was inhibited. In the posterior pituitary gland, D-aspartate inhibited GABA release but had no effect on dopamine or alpha-MSH release. We report that D-aspartate differentially affects the release of hypothalamic and posterior pituitary factors involved in the regulation of pituitary hormone secretion.
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PMID:The effect of D-aspartate on luteinizing hormone-releasing hormone, alpha-melanocyte-stimulating hormone, GABA and dopamine release. 1248 23


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