UNIPROT:P01189 - FACTA Search

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)

This review of the CNS effects of the neurohypophyseal hormones and related neuropeptides discusses recent data illustrating the significance of these principles in brain function, synthesis, distribution, in particular in extrahypothalamic brain structures, binding sites, and signal transduction. Binding sites for vasopressin of the vascular V1a type have been found in the CNS and there is evidence for the existence of a subtype of the antidiuretic V2 receptor in the brain. Also two types of oxytocin binding sites have been detected. One widely distributed throughout the CNS is comparable to the uterine type receptor and a sexually dimorphic slightly different type is found in the ventromedial nucleus. Vasopressin and oxytocin can be converted to highly selective C-terminal fragments as AVP-(4-9) and OXT-(4-9) and shorter fragments. Conversely they can be acetylated. This almost completely blocks intrinsic activity in bioassays for central and peripheral effects. Such modifications are a good example of the plasticity of a neuropeptide system. For a number of CNS effects of the neurohypophyseal hormones, the whole molecule is required, as it is for their endocrine effects. This is the case for the influence of vasopressin on social communication, temperature regulation, epilepsy, and barrel rotation which may be an animal model of febrile convulsions, and some aspects of the central regulation of the cardiovascular system and for oxytocin on sexual behavior, social communication, and grooming. Nonendocrine C-terminal conversion products seem to exert their effects exclusively on the brain. These neuropeptides modulate learning and memory processes, social recognition, and rewarded behavior. The neuroendocrine and neuropeptide effect of vasopressin and oxytocin and related neuropeptides often exert their CNS effects in an opposite way. Neurochemical and electrophysiological studies suggest that norepinephrine, dopamine, serotonin, and glutamate are the neurotransmitters involved in the influence of the neurohypophyseal hormones and related neuropeptides on brain function. It appears that adequate amounts of vasopressin and oxytocin to induce these effects are released at the appropriate sites of action. It is postulated that the mix of neuropeptides released in the brain in response to environmental changes qualifies the behavioral, neuroendocrine, and immune response and the response of the autonomic nervous and vegetative systems of the organism. Although various other neuropeptides, such as those colocalized in vasopressinergic and oxytocinergic neurons, those produced in pro-opiomelanocortin (POMC) systems, and others, play a role in the modulation of adaptive responses, the neurohypophyseal hormones are unique in that their production sites in the hypothalamus serve the periphery, the pituitary, and the brain.
...
PMID:Central nervous system effects of the neurohypophyseal hormones and related peptides. 825 77

Adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) injected i.c.v. induce so called 'excessive grooming'. Whether these peptides play a role in the initiation of grooming is not clear, since rats will groom even as a consequence of a particular environmental stimulation, such as handling and/or a novel environment. In most studies, therefore, the first 15 min after i.c.v. injection are not examined. Here we report on the effects of slow i.c.v. infusions of ACTH-(1-24), alpha-MSH and oxytocin in resting rats in their home cages. Interestingly, i.c.v. infusions of oxytocin did initiate grooming in a dose-related way. In contrast, i.c.v. infusions of both ACTH-(1-24) and alpha-MSH in resting rats were without effect on grooming. Oxytocin is apparently involved in the initiation of self-grooming in rats, whereas ACTH and alpha-MSH prolonged grooming initiated by other means, e.g. handling procedures and/or a novel environment. We conclude that the effects of alpha-MSH and ACTH on grooming are conditional, depending on the behavioural state (active or resting) of the animal.
...
PMID:Induction of grooming in resting rats by intracerebroventricular oxytocin but not by adrenocorticotropic hormone-(1-24) and alpha-melanocyte-stimulating hormone. 838 17

The present study was designed to discriminate between factors that initiate and/or prolong self-grooming. The study of factors initiating the grooming response is complicated by the fact that rats may groom already as a consequence of the injection procedure, due to release of endogenous substances after needle insertion or just handling of the animal. Therefore we used an infusion technique that allowed the rats to settle down quietly after they had been connected to an infusion pump, before the actual infusion of the peptide took place. In a previous report, we showed that direct injections of ACTH1-24 and alpha-melanocyte-stimulating hormone (alpha-MSH) into the paraventricular nucleus of the hypothalamus (PVH) prolong self-grooming caused by the injection procedure. Whether these peptides can also initiate grooming, however, is not yet clear. In this report, we compare the effects of alpha-MSH and oxytocin after infusion into the PVH in resting animals. Oxytocin is abundantly present in the PVH and is known to be involved in the regulation of grooming behavior. Slow infusions of oxytocin (0.1 microgram) do initiate grooming, but alpha-MSH (0.1 microgram) is without any behavioral effect. This suggests that oxytocin in the PVH is involved in the initiation of self-grooming, whereas alpha-MSH and probably ACTH do maintain grooming initiated otherwise, either by mechanical activation of the PVH and/or by the handling procedures. Infusion of substances in resting animals apparently is a way to avoid interactions between ongoing overt behavior and peptide-induced effects.
...
PMID:Initiation of self-grooming in resting rats by local PVH infusion of oxytocin but not alpha-MSH. 838 71

Oxytocin is secreted during parturition to stimulate myometrial contractions and birth. Prior to the start of labour, oxytocin neurones undergo changes to prepare for optimal secretion during labour. Thus, during late pregnancy oxytocin secretion is limited by endogenous opioid inhibition. This does not appear to act at the oxytocin nerve terminals in the neural lobe since they in fact become desensitised to opioid inhibition, responding less to either the general opioid antagonist, naloxone, or to the specific kappa-opioid agonist U50,488, and kappa-receptor binding decreases. However, removal of opioid inhibition on oxytocin neurones by naloxone activates oxytocin cell bodies and there is an increase in the number of cells expressing Fos protein in the supraoptic nucleus. This action is mediated via mu- and not kappa-opioid receptors since norBinaltorphimine (kappa-antagonist) is ineffective. Endogenous opioids are likely to act pre-synaptically on inputs to oxytocin neurones, especially those from the brainstem since naloxone potentiates the firing rate response of oxytocin neurones to intravenous cholecystokinin administration which acts via noradrenergic neurones. The endogenous opioid, beta-endorphin may be responsible for inhibition of oxytocin neurones as both the peptide content and its precursor proopiomelanocortin mRNA content increase in the arcuate nucleus during pregnancy, whereas expression of the co-localized opioids, prodynorphin or proenkephalin A, in magnocellular neurones does not alter.
...
PMID:Pathways to parturition. 871 93

procedure previously shown to inhibit oxytocin release and milk ejection. Two control milkings were performed in familiar surroundings. After milk flow had ceased, two i.v. injections of 1 i.u. oxytocin were given to remove the remaining milk. Milk flow was recorded continuously and blood samples were taken every minute during milking and 10 min after milking. During the first milking in unfamiliar surroundings, no oxytocin was released. Thereby, only 13 percent of the total milk yield, the cisternal milk, was available and the alveolar milk fraction could only be removed after injection of oxytocin. During subsequent relocations oxytocin release steadily increased toward the control level, although the timing of oxytocin release remained delayed as compared with controls. However, the milk fraction available before oxytocin injection increased with increasing number of removals, following an asymptotic approach to control levels. The concentrations of beta-endorphin, cortisol (and perhaps also of prolactin) gradually declined with the number of times the animal was moved to unfamiliar surroundings, i.e. hormone concentrations gradually adjusted to control level. During milking, concentrations of prolactin and cortisol increased, while beta-endorphin concentrations decreased (except for the first relocation). We conclude that milking-related oxytocin release and therefore milk ejection adapted gradually to repeated relocations to unfamiliar surroundings. This adaptation was inversely related to beta-endorphin concentrations, so it is possible that oxytocin release was suppressed by high circulating beta-endorphin concentrations.
...
PMID:Milk yield, oxytocin and beta-endorphin gradually normalize during repeated milking in unfamiliar surroundings. 886 43

Oxytocin (OXT), a neurohypophyseal hormone, has a wide range of behavioral effects outside its classic peripheral endocrine functions. OXT involvement in adaptive central nervous system processes has been demonstrated as an inhibitory, amnestic action on learning and memory in different paradigms. Because adaptation and learning are likely to be involved in the neural events leading to drug tolerance and dependence, the question logically arose whether OXT is able to influence the development of tolerance of and dependence on abused drugs. In this review, we summarize our results on the effects of OXT on opiate (including morphine, heroin, and the endogenous opiates beta-endorphin and enkephalin) tolerance and dependence, heroin self-administration, psychostimulant-induced behavioral changes, and behavioral tolerance and sensitization. The sites and mechanisms of action and the possible physiological role of OXT are also discussed. In the first part of this review the effects of exogenously administered OXT on both the acute and chronic behavioral effects of opiates and psychostimulants have been summarized. OXT inhibited the development of tolerance to morphine, heroin, beta-endorphin, and enkephalin, OXT also inhibited the development of cross-tolerance between the predominantly mu-agonist heroin and the predominantly delta-agonist enkephalin in mice. Naloxone-precipitated morphine withdrawal syndrome was also attenuated by OXT. Heroin self-administration was decreased by OXT administration in heroin-tolerant rats. OXT inhibited cocaine-induced exploratory activity, locomotor hyperactivity, and stereotyped behavior in rats and in mice. Behavioral tolerance to cocaine was also attenuated by OXT. On the contrary, OXT stimulated the development of behavioral sensitization to cocaine. OXT did not alter the stereotyped behavior induced by amphetamine. In the second series of experiments, the sites of action of OXT on drug-related behavior were investigated. Intracerebro-ventricular (ICV) and intracerebral (IC) administration of an OXT-receptor antagonist inhibited the effects of peripherally administered OXT on morphine tolerance, heroin self-administration, and cocaine-induced sniffing behavior. This suggests the central, intracerebral location of OXT target sites. Local IC microinjection of OXT in physiological doses into the posterior olfactory nucleus, tuberculum olfactorium, nucleus accumbens, central amygdaloid nucleus, and the hippocampus inhibited the development of tolerance to and dependence on morphine as well as cocaine-induced sniffing behavior and tolerance to cocaine. The physiological role of endogenous OXT in acute morphine tolerance has also been demonstrated, since OXT antiserum (ICV) and OXT-receptor antagonist (injected into the basal forebrain structures) potentiated the development of morphine tolerance. Finally, we investigated the possible mechanisms of action of OXT on drug related behavior. Both morphine tolerance and dependence, and cocaine administration, increased dopamine utilization in the mesencephalon and in the nucleus accumbens, respectively. OXT treatment decreased the alpha-methylparatyrosine-induced dopamine utilization in the mesencephalon and in the nucleus accumbens-septal complex. Chronic OXT treatment decreased the number of apparent binding sites of dopamine in the basal forebrain area. It also inhibited a cocaine-induced increase in dopamine utilization in the nucleus accumbens, but not in the striatum. In light of this information, it appears that OXT inhibits the development of opiate tolerance, dependence, and self-administration as well as the acute behavioral actions of and chronic tolerance to cocaine. This suggests the possible role of this neuropeptide in the regulation of drug abuse. Therefore, OXT may act as a neuromodulator on dopaminergic neurotransmission in limbic-basal forebrain structures to regulate adaptive CNS processes leading to drug addiction.
...
PMID:Role of oxytocin in the neuroadaptation to drugs of abuse. 921 Feb 15

Since the pineal-neurohypophysial interactions are now well established and oxytocin secretion is known to be a component of the neuroendocrine response to the majority of stressful stimuli, the present experiments were undertaken to estimate whether melatonin modifies the response of oxytocinergic neurons to the immobilization stress. Oxytocin (OT) content in the hypothalamus and neurohypophysis as well as plasma level of OT, prolactin (PRL) and adrenocorticotropin (ACTH) were studied after melatonin treatment in sham-operated or pinealectomized male rats. In sham-operated rats, melatonin diminished the hypothalamic OT content as well as plasma OT and PRL concentrations, but was without effect on neurohypophysial OT and plasma ACTH levels in otherwise not treated rats. In both wehicle- or melatonin-treated rats, food and water deprivation did not affect the OT, PRL and ACTH secretion. Under stress conditions, however, pituitary OT storage was diminished in vehicle-treated rats and melatonin augmented this response of OT to stress. Melatonin also diminished the PRL and ACTH secretion into the blood in stressed rats. In pinealectomized animals neither hypothalamo-neurohypophysial OT content nor plasma OT, PRL or ACTH concentrations were modified by melatonin treatment in animals otherwise not treated or in those deprived of food and water for 24 hrs. However, melatonin increased the pituitary oxytocin content as well as plasma OT and ACTH concentrations in immobilized animals. Plasma PRL concentration was diminished after melatonin treatment in stressed rats. The results suggest that the response of oxytocinergic neurons to immobilization stress is augmented by melatonin. The effect of melatonin on the OT, PRL and ACTH secretion is modified by pinealectomy.
...
PMID:Melatonin affects the oxytocin and prolactin responses to stress in male rats. 959 18

Oxytocin (OT) stimulates corticotroph function in adult sheep, however, there is little information on OT synthesis and its potential involvement in hypothalamo-pituitary-adrenal (HPA) function in the fetus. The objectives of this study were to examine developmental changes in hypothalamic OT synthesis and to investigate the actions of OT on fetal corticotroph function. Hypothalami were removed at various stages of pre- and post-natal development. OT mRNA levels were measured using in situ hybridization. For in vitro studies, fetal pituitaries were removed on days 129 and 138 of gestation. Anterior pituitary cells were dispersed and cells were treated with different concentrations and combinations of OT, corticotrophin-releasing hormone (CRH), vasopressin (AVP) and cortisol. OT mRNA was present in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by day 60 of gestation, and levels significantly increased at term. OT mRNA was present in parvocellular and magnocellular fields of the PVN. In vitro, OT stimulated adrenocorticotropin (ACTH) output in a dose-dependent fashion, but had no effect on cellular pro-opiomelanocortin (POMC) mRNA levels. There was no significant difference in corticotroph responsiveness to secretagogues between cells harvested at gestation day 129 or gestation day 138. Simultaneous exposure to CRH and OT stimulated increases in ACTH output that were significantly greater than for OT or CRH alone. However, no similar synergistic interaction existed between OT and AVP. Cortisol attenuated OT-stimulated ACTH output. In conclusion, hypothalamic OT mRNA increases at term and OT can stimulate ACTH output from fetal corticotrophs. Together, these data indicate that OT may be involved in the regulation of ACTH secretion in fetal sheep in late gestation.
...
PMID:Hypothalamic oxytocin in the developing ovine fetus: interaction with pituitary-adrenocortical function. 1002 35

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.
...
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.
...
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

<< Previous 1 2 3 4 5 Next >>