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 distribution of the endorphins, beta-endorphin and enkephalin (Met5-enkephalin and Leu5-enkephalin), was determined in the pars distalis, intermedia, and nervosa of the rat pituitary using both immunocytochemical and radioimmunological methods. Immunoreactive (ir) beta-endorphin was found in pars distalis and pars intermedia. On gel filtration of the pars distalis extracts, beta-endorphin immunoreactivity was eluted in three peaks corresponding to pro-opiocortin (5%), beta-lipotropin (75%), and beta-endorphin (20%). beta-Endorphin was the only component in the pars intermedia. Enkephalin was found in high amount in the pars nervosa. A new enkephalinergic hypothalamic-pars nervosa pathway was observed. Dehydration experiments on normal rats and analysis of the genetically polyuric Brattleboro rat suggest that this enkephalinergic pathway may modulate neurohypophyseal neurosecretion.
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PMID:Distribution of opioid peptides in the pituitary: a new hypothalamic-pars nervosa enkephalinergic pathway. 610 25

Intracerebroventricular (i.v.t.) administration of beta-endorphin or leucine5-enkephalin inhibited drinking behavior, the pressor response and increased plasma vasopressin concentration stimulated by an acute elevation in CSF sodium chloride concentration (10 microliter, 1 M NaCl i.v.t.). These effects of endogenous opioid peptides were prevented by naloxone, indicating opiate receptors were required for the biologic response. Drinking behavior associated with regulatory stimuli operant during dehydration was also inhibited by opioid peptides. beta-Endorphin (i.v.t.) delayed the onset and/or reduced the volume of water consumed in response to hypertonic sodium chloride (relative cellular dehydration), polyethylene glycol (hypovolemia) and food-associated drinking behavior. Inhibition of drinking did not appear related to sensory-motor dysfunction as another motivated behavior, eating (onset, amount consumed) was unaffected by beta-endorphin. It is concluded from these results that centrally administered endogenous opioid peptides inhibit sodium chloride-stimulated cerebral mechanisms affecting blood pressure and hydration.
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PMID:Effects of centrally administered endogenous opioid peptides on drinking behavior, increased plasma vasopressin concentration and pressor response to hypertonic sodium chloride. 626 92

The levels of dynorphin-(1-13), leucine enkephalin, beta-endorphin and vasopressin immunoreactivity (ir-DYN, ir-1-ENK, ir-beta-END, ir-VP) have been determined in the anterior and in the neurointermediate lobes of the pituitary of rats subjected to a variety of manipulations. Dehydration of rats by 5 days enforced inhibition of a 2% solution of NaCl resulted in a significant decrease in the levels of ir-DYN, ir-1-ENK and ir-VP, but not in those of ir-beta-END in the neurointermediate lobe of the pituitary. In contrast, substitution of drinking water by a solution containing 20 microgram/ml dexamethasone for 5 days produced a significant increase in the neurointermediate pituitary content of ir-DYN, ir-1-ENK and ir-VP, whereas levels of ir-beta-END remained unaffected. This treatment, however, resulted in a significant fall in the ir-beta-END content of the adenopituitary without changing levels of ir-DYN in this structure. Adrenalectomy was associated with a significant decrease in the ir-DYN, ir-VP and ir-1-ENK content of the neurointermediate lobe of the pituitary and a pronounced elevation in the ir-beta-END but not ir-DYN content of the adenohypophysis. These observations are indicative that the regulation mechanisms of the functional state of particular endorphins differ between the anterior and neurointermediate lobes of the pituitary. The concomitant alterations in levels of ir-DYN, ir-1-ENK and ir-VP detected suggest that a common or similar mechanism of regulation may exist for these peptides. A common biosynthetic origin, however, appears to be unlikely, since Brattleboro rats which are unable to synthesize vasopressin possess unchanged ir-DYN- and ir-1-ENK- levels in the pituitary.
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PMID:Levels of dynorphin-(1-13) immunoreactivity in rat neurointermediate pituitaries are concomitantly altered with those of leucine enkephalin and vasopressin in response to various endocrine manipulations. 627 85

The presence of opioid peptides and opiate receptors in the hypothalamo-neurohypophysial system, as well as the inhibitory effects of enkephalins and beta-endorphin on release of oxytocin and vasopressin have been well documented. The physiological importance of opioid peptides in this classical neurosecretory system, however, has remained illusive. In the present study we tested the effects of naltrexone on the plasma concentrations of oxytocin and vasopressin during dehydration, hemorrhage and suckling in the conscious rat. We obtained evidence supporting the hypothesis that opioid peptides inhibit oxytocin release and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Our data support the concept that the coexistence of a neuromodulator and a neurohormone in the same neuron, as demonstrated for vasopressin with dynorphin or leucine-enkephalin, serves to regulate the differential release of two biologically different, yet evolutionarily-related, neurohormones, e.g. oxytocin and vasopressin, from the same neuroendocrine system.
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PMID:A functional role for opioid peptides in the differential secretion of vasopressin and oxytocin. 654 Oct 75

In the present study, we used subcutaneous polyethylene glycol injections to show that a physiologically relevant stimulus, hypovolemia, will selectively increase the expression of neuropeptide genes in a restricted population of parvicellular corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Our results show that a large reduction in extracellular fluid maintained over approximately 20 hours is associated with a significant increase in the level of corticotropin-releasing hormone mRNA in the medial parvicellular division of the paraventricular nucleus. Additionally, there are concomitant increases in cellular levels of both neurotensin/neuromedin N and proenkephalin mRNAs. Our colocalization results show that the increases in neurotensin/neuromedin N and proenkephalin mRNAs after polyethylene glycol injection occur to a significant degree in cells that also contain corticotropin-releasing hormone mRNA. Furthermore, significant numbers of cells containing proenkephalin mRNA also contain neurotensin/neuromedin N mRNA, raising the possibility that some neurons have increased levels of all three mRNAs. Finally, in the medial parvicellular division of the paraventricular nucleus, the number of identified corticotropin-releasing hormone neurons also containing vasopressin mRNA is very low in control animals and is not increased by polyethylene glycol injections, suggesting that, within this period, activation of the vasopressin gene may not be a critical event in the neuroendocrine response of corticotropin-releasing hormone neurosecretory neurons to extracellular dehydration. Considered together with the effects of adrenalectomy on peptide colocalization, our results suggest the existence of several phenotypically distinct sets of neurons within the medial parvicellular division of the paraventricular nucleus, each characterized by its ability to regulate the expression of neuropeptide genes in a stimulus-specific manner.
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PMID:Physiological regulation of peptide messenger RNA colocalization in rat hypothalamic paraventricular medial parvicellular neurons. 772 97

The authors have demonstrated in rats that the ingestion of hypertonic saline for 5 days provides an increasingly complex dehydrating stimulus to the rats. Initially, the stimulus leads to cellular dehydration, but extracellular dehydration develops as ingestion continues beyond 3 days. The initial cellular dehydration provokes modifications to corticotropin-releasing hormone and neurotensin/neuromedin N messenger RNAs (mRNAs) in some neurons of the limbic forebrain, changes that are either maintained or are modified as extracellular dehydration develops. These changes in mRNA content occur in neurosecretory neurons as well as in neurons in hypothalamic and telencephalic regions associated with behavior and autonomic regulation. The authors propose that alterations in peptide mRNAs are allied to altered neuronal signaling processes that direct the different components of the homeostatic response to dehydration.
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PMID:Neuropeptides and thirst: the temporal response of corticotropin-releasing hormone and neurotensin/neuromedin N gene expression in rat limbic forebrain neurons to drinking hypertonic saline. 874 64

We have previously shown that histaminergic neurons participate in mediation of the prolactin (PRL), adrenocorticotropin (ACTH) and oxytocin responses to physiological stimuli such as stress and dehydration. Since suckling is a potent stimulus for the secretion of these three hormones, we investigated the mediating role of neuronal histamine in suckling-induced release of oxytocin, PRL and ACTH in conscious lactating rats. The animals were pretreated with the histamine synthesis inhibitor alpha-fluoromethylhistidine, the H1 receptor antagonist mepyramine, the H2 receptor antagonist cimetidine or the H3 receptor agonist R (alpha) methylhistamine, which by binding to H3 autoreceptors inhibits histamine release and synthesis. After the lactating rats were separated from their pups for 240 min, the pups were returned for a suckling period of 20 min. Thereafter the mothers were sacrificed by decapitation and trunk blood was collected for determination of hormones. Lactating rats not exposed to suckling served as controls. Suckling increased oxytocin 2-fold, PRL 50-fold and ACTH 5-fold. Blockade of histamine synthesis by alpha-fluoromethylhistidine or histamine release by R(alpha)methylhistamine reduced the suckling-induced secretion of the three hormones significantly. Blockade of postsynaptic H1 receptors by mepyramine inhibited the hormone responses to suckling, while the blockade of postsynaptic H2 receptors by cimetidine decreased the suckling-induced oxytocin and PRL release but did not affect the ACTH release. None of the compounds affected oxytocin, PRL or ACTH secretion in lactating mothers not exposed to suckling. In addition, suckling significantly increased the mRNA of the histamine synthesizing enzyme histidine decarboxylase in the ventrolateral tuberomammillary nucleus by 1.5-fold, indicating that the stimulus of suckling enhances the neuronal histamine synthesis. We conclude that suckling increases neuronal histamine synthesis and that histaminergic neurons by activation of postsynaptic H1 and H2 receptors are involved in the hypothalamic mediation of oxytocin, PRL and ACTH responses to suckling. These findings further substantiate a role of neuronal histamine in the neuroendocrine regulation of pituitary hormones in response to physiological stimuli.
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PMID:Involvement of histamine in suckling-induced release of oxytocin, prolactin and adrenocorticotropin in lactating rats. 879 97

We have previously shown in dehydrated rats that cellular levels of the mRNAs encoding the precursor peptides for corticotropin-releasing hormone and neurotensin/neuromedin N significantly increase in a restricted region of the lateral hypothalamic area (Watts, 1992, Brain Res. 581:208-216). The experiments reported here address the role that forebrain osmosensitive cells groups or regions associated with autonomic regulation play in developing this mRNA response. The first experiment showed that unilateral knife cuts placed between the rostral forebrain and the lateral hypothalamic area (LHA) will unilaterally attenuate the mRNA response in the LHA to dehydration. In a second experiment, small injections of the retrograde tracer Fluorogold into the region of the LHA containing these mRNAs revealed a direct input from the osmosensitive median preoptic nucleus and subfornical organ and from the fusiform nucleus of the bed nuclei of the stria terminalis, which is part of a complex of cell groups associated with autonomic regulation. We found that at least 30% of the neurons in the median preoptic nucleus and subfornical organ and 14% of the neurons in the fusiform nucleus of the bed nuclei of the stria terminalis that project to the LHA responded to a rapid increase in plasma osmolality with increased c-fos mRNA levels. In the final experiment, injections of Fluorogold into the LHA were made simultaneously with ipsilateral rostral knife cuts. Here the numbers of neurons accumulating Fluorogold in the median preoptic nucleus, subfornical organ, and the fusiform nucleus were all significantly decreased concomitantly with attenuated mRNA responses in the LHA to dehydration. We conclude that the LHA receives direct and functional projections from the median preoptic nucleus, subfornical organ, and the fusiform nucleus. These projections appear capable of mediating a substantial part of the response of peptidergic mRNAs in the LHA to dehydration.
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PMID:Mediation of dehydration-induced peptidergic gene expression in the rat lateral hypothalamic area by forebrain afferent projections. 880 32

The article reviews some of the recent work showing how physiological stimuli act to alter neuropeptide gene expression. It describes how neural and humoral factors activated by physiological stimuli interact with the mechanisms regulating neuropeptide gene expression in neurons with either vascular (neurosecretory) or cellular (centrally directed) synapses. Although the focus will be on corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus, comparisons will be made between this neurosecretory cell group and others that express this gene. The regulation of neuropeptide genes colocalized in neurons that synthesize CRH is also considered. The review begins with a brief historical introduction, placing peptides in the overall functional perspective of neurosecretory and centrally directed neurons. It then describes studies using in vitro preparations that reveal details of the signal transduction mechanisms responsible for altering the expression of neuropeptide genes. For the CRH gene they are providing the foundations for future work on how physiological stimuli alter mRNA levels in the whole animal. Physiological stimuli provide a very broad range of signals to neuropeptide neurons commensurate with the wide variety of motor responses they initiate. One important humoral signal impacting neuropeptide neurons is plasma corticosterone, and many workers have addressed this aspect of its function. Corticosterone appears capable of interacting with at least two different neuronal mechanisms to regulate CRH mRNA levels: one is clearly seen in paraventricular neurosecretory neurons, where increasing plasma corticosteroid reduces CRH mRNA levels; the other, seen in neurons in the central nucleus of the amygdala, acts to increase them. Since physiological stimuli present a complex mixture of humoral and neural signals to the CNS, integration of these two signal types is a critical aspect of peptide metabolism that requires detailed attention. Studies that are beginning to address this important question are described. Circadian influences play an important role in organizing homeostatic processes, and their influence on CRH gene expression is considered. The viscerosensory-motor integration associated with dehydration offers a useful model for investigating the role of peptides in neuronal function and motor architecture. Much of our work has concentrated on how peptide genes are regulated by alterations to fluid homeostasis, and these studies, along with those of other investigators, are described in this integrative context. Finally, consideration is given to the many studies that have addressed the impact of nonviscerosensory stimulation on neuropeptide gene expression.
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PMID:The impact of physiological stimuli on the expression of corticotropin-releasing hormone (CRH) and other neuropeptide genes. 881 98

Stress stimulates the secretion of the pro-opiomelanocortin (POMC) derived peptides ACTH and beta-endorphin (beta-END) as well as prolactin (PRL) from the adenohypophysis. The regulation of adenohypophysial hormone secretion is complex and includes a variety of neuropeptides and neuroamines. Histamine (HA) seems to participate as a neurotransmitter in the central regulation of adenohypophysial secretion and is involved in stress-induced release of these hormones. However, the effect of HA on POMC and PRL secretion is indirect and may involve activation of hypothalamic neurons subsequently releasing hypophysiotropic factors that in turn regulate adenohypophysial hormone secretion. In addition to the major hypothalamic factors regulating POMC and PRL secretion, corticotropin-releasing hormone and dopamine, the neurohypophysial peptides arginine-vasopressin (AVP) and oxytocin (OT) may serve such a regulatory role in adenohypophysial hormone secretion. We investigated this hypothesis at two different levels by a series of experiments presented in this review. The experiments aimed at studying: 1) the possible role of HA as a neuroendocrine regulator of AVP and OT secretion and neuronal activation, and 2) the possible involvement of AVP and OT in physiological regulation of POMC derived peptide and PRL secretion. In the first part of the study we found HA to be an important regulator of vasopressinergic and oxytocinergic neuronal activity and of AVP and OT secretion. The effect of HA is mediated via activation of both HA H1- and H2-receptors. The regulatory role of HA on the neuronal AVP and OT system is of physiological relevance since it is important for the adequate AVP and OT response to physiological stimuli such as dehydration and suckling. In the second part of the study we found that secretion of POMC derived peptides and PRL in response to stress and HA is transmitted via AVP but not via OT. The effect of AVP in HA- and stress-induced POMC and PRL secretion is both mediating and permissive and the AVP-receptors involved differ with respect to these two actions as well as with type of adenohypophysial hormone secreted.
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PMID:Neurohypophysial peptides. Histaminergic regulation and function in adenohypophysial secretion. 896 Aug 13


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