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 present study was undertaken to investigate whether beta-adrenoceptors are involved in regulation of yawning responses to oxytocin and alpha-melanocyte-stimulating hormone (alpha-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. alpha-MSH (20 micrograms/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M1 receptor agonist, administered ICV at a lower dose of 100 micrograms/rat and subcutaneously (SC) at doses of 0.25-2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by alpha-MSH (20 micrograms/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)5,Tyr(Me)2,Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, alpha-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a mucarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and alpha-MSH is modulated by beta-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.
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PMID:Involvement of beta-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and alpha-melanocyte-stimulating hormone, in rats. 761 71

gamma-Melanocyte-stimulating hormone (gamma-MSH), atrial natriuretic peptide (ANP), and oxytocin have been identified as candidate hormonal mediators of the reflex natriuresis that follows acute unilateral nephrectomy (AUN). Pharmacological characterization of the third melanocortin receptor (MC3-R) indicates that it uniquely responds to physiological concentrations of gamma-MSH. We tested the roles of gamma-MSH, ANP, and oxytocin in the postnephrectomy natriuresis by carrying out AUN during continuous intrarenal infusion of specific antagonists for their cognate receptors. In anesthetized Sprague-Dawley rats, urinary sodium excretion (UNaV) increased from 0.34 +/- 0.04 to 1.12 +/- 0.11 mu eq/min 90 min after AUN (P < 0.001). No change in UNaV occurred in rats undergoing a sham AUN procedure. Plasma immunoreactive gamma-MSH concentration was 53 +/- 8 fmol/ml after sham AUN but 112 +/- 17 fmol/ml after AUN (P < 0.01). SHU-9119 and SHU-9005 are substituted derivatives of alpha-MSH with potent antagonism at the MC3-R in vitro. Infusion of these compounds at 5 pmol/min completely blocked the natriuretic response to AUN despite a similar elevation in plasma gamma-MSH (111 +/- 12 vs. 49 +/- 8 fmol/ml in sham rats, P < 0.01). Intrarenal infusion of the ANP receptor antagonist A-71915 (5 pmol/min) or the oxytocin receptor antagonist [d(CH2)(5)1, Tyr(Me)2,Orn8] vasotocin (10 pmol/min) effectively inhibited the natriuresis induced by intravenous infusion of ANP or oxytocin (each at 1 pmol/min), respectively, but did not block the natriuresis after AUN. Plasma immunoreactivity of these peptides was not increased after AUN. These results indicate that reflex natriuresis after AUN is accompanied by an increase in plasma gamma-MSH but not ANP or oxytocin concentration and is prevented by intrarenal infusion of receptor antagonists with selectivity for MC3-R. The data indicate that gamma-MSH or a closely related peptide mediates postnephrectomy natriuresis and provide further support for the possibility that gamma-MSH may play a wider role in sodium homeostasis.
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PMID:Prevention of reflex natriuresis after acute unilateral nephrectomy by melanocortin receptor antagonists. 957 53

The involvement of brain oxytocin in the attenuated responsiveness of the hypothalamo-pituitary-adrenal axis and the oxytocin systems to external stressors found in pregnant and lactating rats has been studied, including both neuroendocrine and behavioural aspects. Intracerebroventricular infusion of an oxytocin receptor antagonist (0.75 microg/5 microl), but not of vehicle, elevated basal corticotropin and corticosterone secretion into blood of virgin female, but not of late pregnant or lactating rats. Oxytocin antagonist treatment further elevated the stress-induced (exposure to the elevated plus-maze or forced swimming) secretion of both corticotropin and corticosterone, but only in virgin and not in pregnant or lactating rats. Thus, corticotropin and corticosterone plasma concentrations remained attenuated in antagonist-treated pregnant and lactating animals. In contrast, infusion of the oxytocin antagonist significantly elevated the stress-induced secretion of oxytocin into blood in pregnant and lactating, but not in virgin, animals, indicating an autoinhibitory influence of intracerebral oxytocin on neurohypophysial oxytocin secretion induced by non-reproduction-related stimuli. Treatment with oxytocin antagonist 10 min prior to behavioural testing on the elevated plus-maze significantly reduced the anxiety-related behaviour in both pregnant and lactating rats, without exerting similar effects in virgin female rats. The results demonstrate a tonic inhibitory effect of endogenous oxytocin on corticotropin and, consequently, corticosterone secretion in virgin female rats, an effect which is absent in the peripartum period. In contrast, an anxiolytic action of endogenous oxytocin was detectable exclusively in pregnant and lactating rats. Therefore, we conclude that the actions of intracerebral oxytocin include independent effects on the responses of the hypothalamo-pituitary-adrenal axis and oxytocin systems to stressors and the anxiety-related behaviour which are modulated by the reproductive state of the animals.
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PMID:Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-related behaviour in virgin, pregnant and lactating rats. 1065 37

Oxytocin is a classic reproductive neuropeptide in the female mammal, but its functions in the brain of the male have been less well studied. As stress induces intracerebral oxytocin release independently of gender, we postulated that central oxytocin may play a role in the control of stress responses. In both male and virgin female rats, oxytocin receptor blockade in the brain by intracerebral infusion of a selective oxytocin antagonist (des Gly-NH2 d(CH2)5 [Tyr(Me)2, Thr4] OVT; 0.75 microgram/5 microliter increased the activity of the hypothalamo-pituitary-adrenal (HPA) axis as indicated by a significantly enhanced basal and stress-induced (exposure to the elevated plus-maze, forced swimming) secretion of corticotropin (ACTH) and corticosterone into blood. The anxiety-related behaviour on the plus-maze was not altered by the antagonist in either males or females. Infusion of the oxytocin antagonist into the hypothalamic paraventricular nucleus by reversed microdialysis resulted in a significant increase in basal release of ACTH in both male and virgin female rats. These results demonstrate a novel, gender-independent physiological function of endogenous brain oxytocin in the regulation of neuroendocrine stress responses. Under basal conditions, the inhibition of the HPA axis occurs, at least in part, within the paraventricular nucleus.
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PMID:Brain oxytocin inhibits basal and stress-induced activity of the hypothalamo-pituitary-adrenal axis in male and female rats: partial action within the paraventricular nucleus. 1071 19

Regulation of pituitary vasopressin V1b receptors plays a critical role in regulating pituitary adrenocorticotropic hormone (ACTH) secretion during adaptation to stress. The objective of this study was to isolate the promoter regulatory region of the V1b receptor gene to better understand the molecular mechanisms involved in V1b receptor regulation. Screening of a rat genomic library using probes directed to the coding region and to the 5'UTR of the rat V1b receptor resulted in the isolation of several clones containing the 5'upstream regions of the V1b receptor cDNA. Sequencing of an 11.2 Kb fragment revealed 8.2 Kb upsteam of the reported cDNA sequence, which contains a putative promoter regulatory region. The 3' end of the clone contained 1472 base pairs corresponding to the recognized cDNA sequence, followed by 1506 bp of unknown sequence located at the end of the sixth transmembrane domain, probably corresponding to an intron, characteristic of these family of receptors. An additional 161 bp intron was found in the 5'UTR, similar to that described in the rat oxytocin receptor gene. 5'RACE and RNase protection analysis mapped two major putative transcription start points at -830 and -861 bp from the starting methionine. Analysis of the putative promoter region showed no indication of a proximal TATA box, but the presence of a CACA box, a GAGA box, several AP-1 and AP-2 sites and a cluster of Sp1 sites upstream of the AP-2 sites. A luciferase construct containing a 2.1-kb of putative promoter, and part of the 5'UTR including the first intron, showed promoter activity when transfected into COS-7, CHO and PC12 cell lines but not in AtT-20 cells. A similar construct without the intron and distal 5'UTR sequence has no promoter activity in the same cell lines. In summary, the V1b receptor gene contains at least 3 exons and 2 introns. The 5'flanking sequence contains several potential sites for transcriptional regulation, and induced luciferace activity only in constructs containing intron 1, suggesting that the latter is important for receptor gene activation. The data provide bases for future analysis of the regulatory elements controlling V1b receptor transcription.
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PMID:Isolation and characterization of the promoter region of the rat vasopressin V1b receptor gene. 1079 83

In order to study neuroendocrine and behavioural stress responses in female rats post partum we aimed to establish a relevant emotional stressor -- the maternal defence test based on maternal aggression of a lactating resident towards a virgin or lactating intruder approaching the cage. Exposure to maternal defence significantly elevated corticotropin (ACTH) and corticosterone responses of the residents and of virgin or lactating intruders, with an attenuated response in lactating residents and lactating intruders. Exposure to maternal defence increased plasma oxytocin in virgin intruders only. The aggressive behaviour displayed by the residents was directly correlated with the amount of defensive behaviour of the intruder and independent of the intruder's reproductive state. However, the amount of maternal and explorative behaviours displayed by the lactating residents was significantly higher when exposed to a lactating, compared to a virgin, intruder. ACTH responses in lactating residents exposed to virgin intruders were significantly correlated to the amount of offensive (direct correlation) and maternal (inverse correlation) behaviours they displayed. Plasma prolactin concentrations, elevated in lactating compared to virgin rats under basal conditions, were found to be reduced in the lactating residents and intruders in response to exposure to the maternal defence test, whereas it was unchanged in virgin intruders. To test for the involvement of brain oxytocin in neuroendocrine and behavioural responses of the lactating residents an oxytocin receptor antagonist (0.1 microg/5 microL) was infused icv 10 min prior to testing. This treatment increased basal, but not stress-induced, ACTH, corticosterone and oxytocin secretion. Whereas parameters of aggressive behaviour were unchanged, the antagonist reduced signs of maternal behaviour during maternal defence. In summary, the maternal defence test has been characterized as a relevant emotional stressor for female rats which is useful for studying neuroendocrine and emotional responses in females, in particular in the context of reproductive adaptations.
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PMID:Maternal defence as an emotional stressor in female rats: correlation of neuroendocrine and behavioural parameters and involvement of brain oxytocin. 1126 75

Labour at term and preterm results from activation and then stimulation of the myometrium. Activation can occur through mechanical stretch of the uterus, and by endocrine pathways resulting from increased activity of the fetal hypothalamic-pituitary-adrenal axis. In women and in experimental animals, cortisol likely contributes to increased prostaglandin production in fetal tissues through up-regulation of the type 2 prostaglandin H2, synthase-2 (PGHS-2) and down-regulation of 15-OH prostaglandin dehydrogenase. Cortisol increases expression of prostaglandin dehydrogenase in the chorion by reversing the stimulatory effect of progesterone, and may represent "progesterone withdrawal" in the primate. By competing with progesterone inhibition, cortisol also increases expression of placental corticotropin-releasing hormone. Other agents, such as pro-inflammatory cytokines, similarly up-regulate PGHS-2 and decrease expression of prostaglandin dehydrogenase. Oxytocin, produced locally within the intrauterine tissues, is also thought to be involved in parturition, and there is a marked increase in oxytocin receptor expression at term. There are thus several mechanisms by which labour at term or preterm may be initiated. These different mechanisms need to be considered in the development of strategies for the detection and management of women in preterm labour. Ongoing studies are investigating the use of oxytocin receptor antagonists, PGHS-2 inhibitors, and nitric oxide to prevent or regulate preterm labour. The presence of fibronectin in vaginal secretions, and elevated maternal serum levels of corticotropin-releasing hormone, estrogens, and cytokines have been examined as possible markers of preterm labour. However, at the present time, we do not have the ability to accurately predict or diagnose preterm labour, nor do we have specific or efficient methods to inhibit labour once it has started.
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PMID:Mechanisms of term and preterm birth. 1241

The integration of 'long-term' adiposity signaling with the 'short-term' meal-related signal cholecystokinin (CCK) is proposed to involve descending hypothalamic projections to areas of the caudal brainstem (CBS) that regulate the amount of food consumed during a single meal. One such projection extends from cell bodies in the hypothalamic paraventricular nucleus (PVN) to the nucleus tractus solitarius (NTS), where cells that respond to peripheral CCK are concentrated. Candidate neuronal cell types that may comprise this PVN-NTS projection includes those expressing corticotropin-releasing hormone (CRH) or oxytocin. We therefore sought to determine whether oxytocin or CRH axons are preferentially located in close anatomical proximity to neurons of the NTS that are activated by peripheral administration of CCK, as determined by immunocytochemical staining for Fos protein. Rats received injections of either an anorexic dose of CCK (8 nmol/kg, i.p.) or vehicle and were perfused 2 h later with 4% paraformaldehyde. Immunocytochemistry was performed on cryostat sections (14 microm) of caudal brainstem, using a polyclonal antibody to Fos protein and either a monoclonal antibody to oxytocin or a polyclonal antibody to CRH. As expected, CCK administration significantly increased the numbers of Fos-positive neurons by 489% (p<0.01) and 400% (p<0.01), respectively, in the medial and gelatinosus subdivisions of the NTS. These same regions received dense oxytocin axon innervation, whereas CRH immunoreactivity was not as prevalent in these areas. In areas outside the NTS, such as the dorsal motor nucleus of the vagus (DMV), Fos activation was absent despite a dense oxytocin and CRH innervation. To investigate whether CCK-induced reductions of food intake require intact oxytocin signaling, we performed a separate study in which CCK injection was preceded by injection into the fourth ventricle of an oxytocin receptor antagonist [d(CH(2))(5), Tyr (Me)(2), Orn(8)]-vasotocin (OVT). This study showed CCK was 23% and 22% less effective at inhibiting food intake at 30 min (p<0.05) and 1 h (p<0.05) food intake, respectively, in the presence of OVT. Taken together, the data indicate that oxytocin axons within the descending pathway from the PVN to the NTS are anatomically positioned to interact with NTS neurons that respond to vagally mediated peripheral CCK signals such as those that occur following ingestion of a meal. These findings support the hypothesis that oxytocin exerts a tonic stimulatory effect on the response of key neurons within the NTS to CCK and further reduce meal size.
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PMID:Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin. 1464 28

Arginine vasotocin is a neurohypophysial hormone in lower vertebrates including birds. Its actions are mediated through G-protein coupled receptors that belong to the vasopressin/oxytocin receptor family. Our laboratory recently cloned a vasotocin receptor, designated the VT2 receptor (VT2R), which shares high sequence identity at both the nucleotide and amino acid level with the mammalian V1b vasopressin receptor (V1bR). In the present study, we report development and use of an antibody to the VT2R to obtain anatomical evidence for testing the hypothesis that the VT2R is the avian homolog of the mammalian V1bR. Results verified the specificity of the antibody and demonstrated a receptor distribution occurring predominantly in the cephalic lobe of the pars distalis and co-localizing with adrenocorticotropin in corticotrophs. With respect to VT2R distribution and cell-type localization in pituitary gland, evidence presented support its similarity with the mammalian V1bR. In contrast to the mammalian V1bR, VT2R expression was not observed in chicken brain. Further research will be required to determine which receptor/s in the arginine vasotocin/mesotocin family are expressed in brain and mediate regulatory functions of vasotocin in the central nervous system.
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PMID:Characterization and immunohistochemical visualization of the vasotocin VT2 receptor in the pituitary gland of the chicken, Gallus gallus. 1599 8

Recently, we synthesized and characterized the first selective V(1b) vasopressin (VP)/oxytocin receptor agonist, d[Cha(4)]arginine vasopressin. However, this agonist was only selective for the human receptors. We thus decided to design a selective V(1b) agonist for the rodent species. We started from previous observations showing that modifying [deamino(1),Arg(8)]VP in positions 4 and 8 altered the rat VP/oxytocin receptor selectivity. We synthesized a series of 13 [deamino(1),Arg(8)]VP analogs modified in positions 4 and 8. Among them, one seemed very promising, d[Leu(4), Lys(8)]VP. In this paper, we describe its pharmacological and physiological properties. This analog exhibited a nanomolar affinity for the rat, human, and mouse V(1b) VP receptors and a strong V(1b) selectivity for the rat species. On AtT20 cells stably transfected with the rat V(1b) receptor, d[Leu(4), Lys(8)]VP behaved as a full agonist on both phospholipase C and MAPK assays. Additional experiments revealed its ability to induce the internalization of enhanced green fluorescent protein-tagged human and mouse V(1b) receptors as expected for a full agonist. Additional physiological experiments were performed to further confirm the selectivity of this peptide. Its antidiuretic, vasopressor, and in vitro oxytocic activities were weak compared with those of VP. In contrast, used at low doses, its efficiency to stimulate adrenocorticotropin or insulin release from mouse pituitary or perfused rat pancreas, respectively, was similar to that obtained with VP. In conclusion, d[Leu(4), Lys(8)]VP is the first selective agonist available for the rat V(1b) VP receptor. It will allow a better understanding of V(1b) receptor-mediated effects in rodents.
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PMID:Pharmacological and physiological characterization of d[Leu4, Lys8]vasopressin, the first V1b-selective agonist for rat vasopressin/oxytocin receptors. 1749 6


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