Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our study was designed to study the modulatory role of nitric oxide/cyclic guanosine monophosphate in the spinal cord on the antinociception induced by morphine and beta-endorphin given supraspinally. The antinociception was assessed by the tail-flick test in male ICR mice. The antinociception induced by intracerebroventricularly (i.c.v.) administered morphine was potentiated by intrathecal (i.t) injection of N omega-nitro-L-arginine (2 micrograms), hemoglobin (120 micrograms) or methylene blue (5 micrograms), but was attenuated by i.t. administered L-arginine (20 micrograms) or 3-morpholino-sydnonimine (SIN-1, 5 micrograms). In contrast, the antinociception induced by i.c.v. administered beta-endorphin was attenuated by i.t. pretreatment with N omega-nitro-L-arginine (2 micrograms) and the attenuation of beta-endorphin-induced antinociception by N omega-nitro-L-arginine was reversed by i.t. administered L-arginine (20 micrograms). The antinociception induced by i.c.v. administered beta-endorphin was also attenuated by i.t. administration of hemoglobin (120 micrograms) or methylene blue (5 micrograms). Intrathecal pretreatment with L-arginine did not affect i.c.v. administered beta-endorphin-induced antinociception. It is concluded that the inhibition of nitric oxide/cyclic guanosine monophosphate system in the spinal cord potentiates i.c.v. administered morphine-induced antinociception but attenuates i.c.v. beta-endorphin-induced antinociception. The activation of nitric oxide/cyclic guanosine monophosphate system in the spinal cord attenuates i.c.v. administered morphine-induced antinociception but does not affect i.c.v. administered beta-endorphin-induced antinociception.
 ...
PMID:Nitric oxide/cyclic guanosine monophosphate system in the spinal cord differentially modulates intracerebroventricularly administered morphine- and beta-endorphin-induced antinociception in the mouse. 761 52

Nitric oxide (NO) donors such as sodium nitroprusside (SNP, 0.01-1 micrograms) or 3-morpholino-sydnonimine (SIN-1, 0.1-10 micrograms) administered intracerebroventricularly (i.c.v) produced a dose-dependent potentiation of beta-endorphin-induced antinociception assessed by the tail-flick test in ICR mice. The same i.c.v. treatment with SNP or SIN-1 did not affect the antinociception induced by mu-, delta-, or kappa-opioid receptor agonists. The goal of the present study was to determine if the potentiation of the beta-endorphin-induced antinociception by NO donors is mediated by the activation of NO-cGMP system. Co-administration of hemoglobin (30-120 micrograms) or methylene blue (1.25-5 micrograms), but not N omega-nitro-L-arginine (1-5 micrograms) given i.c.v. dose-dependently attenuated the potentiating effects of SNP or SIN-1 on beta-endorphin-induced antinociception. However, the same i.c.v. treatments of mice with hemoglobin, methylene blue or N omega-nitro-L-arginine did not directly affect the i.c.v. administered beta-endorphin-induced antinociception. On the other hand, the treatment of mice with a combination of NO donor (SNP, 0.1 micrograms or SIN-1, 1 microgram) and zaprinast (a cGMP phosphodiesterase inhibitor, 1 microgram) further potentiated beta-endorphin-induced antinociception. These results indicate that the potentiating effect of SNP or SIN-1 on beta-endorphin-induced antinociception is mediated by the increased production of NO-cyclic GMP in the brain. However, the NO-cGMP system is not directly involved in the beta-endorphin-induced antinociception.
 ...
PMID:Activation of a NO-cyclic GMP system by NO donors potentiates beta-endorphin-induced antinociception in the mouse. 871 39

Corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are two potent stimulators for secretion of proopiomelanocortin (POMC)-derived hormones, from corticotrophs. CRH also stimulates POMC synthesis. Atrial natriuretic peptide (ANP) has been reported to inhibit POMC peptide release and is thought to act through cGMP signalling pathways. A multicolumn cell perifusion system was used to investigate the role of cGMP signalling pathways in CRH- and AVP-stimulated POMC peptide release from primary cultures of ovine or rat anterior pituitary cells. The CRH and/or AVP stimulations were applied at 30 min intervals as 5 min pulses, and the various treatments were infused over a period of 50 min, overlapping with 2 of the stimulations. ANP (10 nM) had no effect on beta-endorphin (betaEP) release from ovine cells, stimulated by 0.5 nM CRH and 5 nM AVP together, or 5 nM CRH and 50 nM AVP separately. Rat anterior pituitary cells were stimulated with 0.05 nM CRH/0.5 nM AVP or 0.5 nM CRH/5 nM AVP and treated with 1 nM or 10 nM ANP, respectively. No inhibition of ACTH or betaEP was observed. Similarly, the nitric oxide donors molsidomine (100 microM), SIN-1 (100 microM) and NaNO2 (100 microM) did not inhibit betaEP release stimulated by 0.5 nM CRH/5 nM AVP in ovine cells. The cGMP analogues 8-bromo-cGMP (10 microM and 100 microM) and dibutyryl cGMP (100 microM) also had no effect on betaEP and ACTH release from ovine or rat anterior pituitary cells. Dexamethasone (8 microM), a synthetic glucocorticoid known to block POMC synthesis and secretion of betaEP and ACTH by a distinct mechanism, was used as a control and suppressed CRH/AVP-stimulated betaEP secretion from ovine anterior pituitary cells. These results contrast with some previous studies and demonstrate that the cGMP signalling pathway in sheep or rat anterior pituitary cells does not directly inhibit secretion of POMC-derived hormones from corticotrophs.
 ...
PMID:Atrial natriuretic peptide, cyclic GMP analogues and modulation of guanylyl cyclase do not alter stimulated POMC peptide release from perifused rat or sheep corticotrophs. 946 18

We investigated the effect of the intracerebroventricular injection of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on the release of adrenocorticotropin hormone (ACTH) and the neuronal response of hypothalamic neurons responsible for this release. Rats that were administered SIN-1 showed significant elevations in plasma ACTH levels, a response that was virtually abolished by antibodies against corticotropin-releasing factor (CRF) and significantly blunted by vasopressin (VP) antiserum. SIN-1 also upregulated heteronuclear (hn) transcripts for CRF and VP and messenger RNA (mRNA) levels for the immediate early gene NGFI-B and for CRF receptor type 1 (CRF-R(1)) in the parvocellular portion of the paraventricular nucleus (PVN) of the hypothalamus. Blockade of prostaglandin synthesis with ibuprofen did not alter the ACTH or the PVN response to SIN-1. The central nucleus of the amygdala and the supraoptic nucleus, regions that are involved in autonomic adjustments to altered cardiovascular activity, also responded to SIN-1 with elevated NGFI-B mRNA levels. However, the only change in mean arterial blood pressure caused by this NO donor was a transient and modest increase. To our knowledge, this is the first demonstration that in the intact rat NO stimulates the activity of PVN neurons that control the hypothalamic-pituitary-adrenal axis. It must be noted, however, that our results do not allow us to determine whether this effect was direct or mediated through PVN afferents. This study should help resolve the controversy generated by the use of isolated brain tissues to investigate the net effect of NO on hypothalamic peptide production.
 ...
PMID:Nitric oxide stimulates ACTH secretion and the transcription of the genes encoding for NGFI-B, corticotropin-releasing factor, corticotropin-releasing factor receptor type 1, and vasopressin in the hypothalamus of the intact rat. 1046 Feb 69

We previously showed that the intracerebroventricular injection of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) released adrenocorticotropic hormone (ACTH) and upregulated transcripts for corticotropin-releasing factor (CRF) and vasopressin in the paraventricular nucleus (PVN) of the rat hypothalamus. In the present work, we microinfused SIN-1 into the PVN itself, the amygdala, the hippocampus or the frontal cortex to identify the brain regions that modulate the influence of NO on the hypothalamic-pituitary-adrenal (HPA) axis. Microinfusion into the PVN, which contains most of the CRF and vasopressin neurones that control HPA axis activity, significantly released ACTH. Microinfusion into the amygdala or the hippocampus, areas which also regulate HPA axis activity, similarly increased plasma ACTH levels. However, these responses were smaller and showed a delayed onset, compared to that observed following PVN treatment. In contrast, microinfusion of SIN-1 into the frontal cortex, which is not believed to exert a major direct influence on the HPA axis, was without effect. The observation that compared to microinfusion into the PVN, peak ACTH levels were both smaller and delayed when SIN-1 was microinfused into the amygdala or the hippocampus, and that SIN-1 only increased NO levels when injected into the PVN, suggests that the NO donor injected outside the PVN activates this nucleus by targeting pathways that connect it to these other regions rather than by leakage. Collectively, our results provide important clues regarding the putative role of these regions in modulating the influence of NO on the HPA axis.
 ...
PMID:Microinfusion of a nitric oxide donor in discrete brain regions activates the hypothalamic-pituitary-adrenal axis. 1173 50

We investigated the ability of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) to release adrenocorticotropic hormone (ACTH) and up-regulate hypothalamic neurones following its intravenous (i.v.) injection. i.v. SIN-1 (0.2-1.8 mg/kg) produced dose-related increases in plasma ACTH levels which were blocked by prior neutralization of endogenous corticotropin-releasing factor (CRF) but not by vasopressin antibodies. In contrast, the intracerebroventricular (i.c.v.) injection of 50-microg SIN-1 released significantly larger amounts of ACTH, a response blunted by either CRF or vasopressin antibodies. While i.c.v. SIN-1 markedly up-regulated transcripts of the immediate early gene NGFI-B in the paraventricular nucleus (PVN) of the hypothalamus, no such response was observed following the i.v. injection of up to 2.0 mg/kg SIN-1. Finally, we found no evidence that the influence of the peripheral administration of SIN-1 on ACTH secretion is mediated by altered pituitary responsiveness to CRF or vasopressin. The fact that NO has a profound hypotensive influence in the periphery suggests that it may have released ACTH through this mechanism, although the absence of PVN neuronal response in regions that are activated by decreased blood pressure casts some doubt on this hypothesis. As the systemic injection of arginine derivatives that block NOS activity potently augment the ACTH response to circulating pro-inflammatory cytokines or vasopressin, the present findings indicate that the mechanisms responsible for this phenomenon are distinct from those responsible for ACTH released by i.v. SIN-1.
 ...
PMID:Comparison between the influence of the intravenous and intracerebroventricular injection of a nitric oxide donor on adrenocorticotropic hormone release and hypothalamic neuronal activity. 1212 94

It has been reported previously that a short synthetic immunomodulating peptide (Pa) and the neuropeptide beta-endorphin modulate the immune system. We have found now that NF-kappaB participates in the stimulation of monocytes by both peptides and we investigated the molecular mechanism by which these stimuli activate NF-kappaB. Pa and beta-endorphin induce accumulation of cyclic 3('),5(')-adenosine monophosphate (cAMP) in a calcium/calmodulin-dependent fashion since it was completely inhibited by the calmodulin antagonist W-7. The effect of these complexes seems to be mediated, at least in part, by nitric oxide (NO) synthesized by constitutive NO synthase since the NO synthase inhibitor N-methyl-L-arginine (NMLA) reduced the elevation of cAMP. Furthermore, the NO donor SIN-1 provoked nitration of G(S)alpha, leading to the cAMP elevation that was suppressed by the G(S)alpha-selective antagonist NF-449. Interestingly, the rapid degradation of NF-kappaB inhibitor IkappaBalpha induced by Pa- and beta-endorphin was reversed by a pretreatment with H-89 and cyclosporin A, inhibitors of protein kinase A (PKA) and protein phosphatase 2B (PP2B), respectively. These observations are consistent with the inhibition caused by W-7, NMLA, H-89, and cyclosporin A on NF-kappaB induction by these agonists, indicating the involvement of PKA and PP2B in the regulation of NF-kappaB in human monocytes.
 ...
PMID:Regulation of NF-kappaB activation by protein phosphatase 2B and NO, via protein kinase A activity, in human monocytes. 1258 44

We investigated the role played by catecholamine-dependent pathways in modulating the ability of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) to release adrenocorticotropic hormone (ACTH) following its intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. We first showed that the nonspecific adrenergic agonist noradrenaline, the alpha- or beta-adrenergic agonists phenylephrine or dobutamine, or the noradrenergic uptake inhibitor desipramine, all significantly stimulated ACTH secretion by freely moving, nonanaesthetized rats. We then observed that destruction of noradrenergic nerve endings with the neurotoxin 6-hydroxydopamine, respectively abolished and significantly decreased the ACTH response to the i.c.v. or i.v. administration of SIN-1. Finally, we sought to identify the type of adrenergic receptor(s) mediating the influence of catecholamines. beta-Adrenergic receptors did not appear to be involved in the stimulatory effect of SIN-1 regardless of its route of injection. By contrast, alpha 2-adrenergic receptors played an important role in the ACTH response to i.v. or i.c.v. administered SIN-1. Collectively, these results indicate that while hypothalamic alpha 1- and beta-adrenergic receptors are important for hypothalamic-pituitary-adrenal (HPA) axis activity, only alpha 2-adrenergic receptors are involved in modulating the ability of NO to release ACTH. Our laboratory and others have previously reported that NO increased hypothalamic noradrenaline levels, while conversely noradrenaline up-regulated levels of NO synthase, the enzyme responsible for NO formation; and that injection of corticotropin-releasing factor into the brain ventricles releases catecholamines and stimulates NO formation. Taken together with these observations, our results point to complex functional relationships between NO, catecholamines and the HPA axis.
 ...
PMID:Role of specific adrenergic receptors in mediating the adrenocorticotropic hormone response to increased nitric oxide levels. 1269 79