Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stress or noxious stimuli of various kind may induce the fight-flight response. In this situation a number of physiological and behavioural adaptations leading to defense of the organism occur. At a central level increased activity in the noradrenergic locus coeruleus (LC) and an enhanced secretion of corticotrophin-releasing factor (CRF) and vasopressin produced in the paraventricular nucleus (PVN) integrate stress response. Here the existence of an opposite psycho-physiological pattern associated with relaxation and growth and which is activated by certain types of non-noxious stimuli and integrated by oxytocin is proposed. In support of this, administration of oxytocin to male and female rats gives rise to effects of antistress nature in particular after repeated administration. Thus a five day treatment period with oxytocin 1 mg/kg s.c. or 1 micro g/kg i.c.v gives rise to sedation, lowering of blood pressure, increased withdrawal latency in the tail flick test and also a decrease of corticosterone levels and a rise of certain vagally controlled hormones. Weight gain is also increased under certain conditions. These effects persist several weeks after administration of oxytocin and cannot be reversed by oxytocin antagonists when established, suggesting that secondary mechanisms have been activated. Naloxone temporarily reverses the increased withdrawal of the tail flick test suggesting that opioid mechanisms have been activated to cause this particular effect. In contrast the sedative and blood pressure lowering effect seems to be induced by an enhanced activity in central alpha 2 receptors. Oxytocin levels increase in blood and CSF after various kinds of non-noxious sensory stimulation such as touch, light pressure and warm temperature in both female and male rats. It is suggested that other types of non-noxious stimuli as well may increase oxytocin release. If so, a release of oxytocin could be responsible for not only the antistress effects occurring during lactation but also why relationships, social contact and networks may have health promoting effects in particular by preventing cardiovascular disease.
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PMID:Oxytocin linked antistress effects--the relaxation and growth response. 940 3

The thymus provides an optimal humoral microenvironment for the development of immunocompetent T cells. Although yolk sac derived pre-T, committed hematopoietic stem cells enter the thymus using a homing receptor, the immigration process also requires secretion of a peptide called thymotaxin by the cells of the reticulo-epithelial (RE) network of the thymic cellular microenvironment. The majority of RE cells have a round or irregular pale nucleus, which contains few, scattered, chromatin granules with a defined, spherical nucleolus, rich in basic histones. Their cytoplasm occasionally displays RNP granules, and is rich in non-histone proteins, fine phospholipid, lipid or cholesterin granules, and vacuoles filled with secreted substances. The cells of the subcapsular, endocrine RE cell layer (giant or nurse cells), characterized by PAS positive granules, express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to medullar RE cells, these subcapsular nurse cells also produce thymosins beta 3 beta 4. Thymic nurse cells (TNCs) display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA-DR) molecule restriction. These cells also contain transforming growth factor-beta (TGF-beta) type II receptors and participate in the positive selection of T cells. Transmission electron-microscopic (TEM) observations have defined four functional subtypes of medullar RE cells: undifferentiated, squamous, villous, and cystic. All subtypes are connected by desmosomes. Immunocytochemical observations have shown that the secreted thymic hormones, thymosin alpha 1 and thymopoietin (and its short form, thymopentin or TP5), are produced by the same RE cells. Thymic RE cells also produce numerous cytokines including IL1, IL6, G-CSF, M-CSF, and GM-CSF that likely are important in various stages of thymocyte activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion, such as growth hormone, prolactin, adrenocorticotropic hormone, thyroid stimulating hormone, triiodothyronine, somatostatin, oxytocin, follicle stimulating hormone, luteinizing hormone, arginine vasopressin, growth hormone releasing hormone, corticotropin releasing hormone, nerve growth factor, vasoactive intestinal peptide, (pro) enkephalin, and beta-endorphin, production of a number of interleukins and growth factors, as well as the expression of receptors for all, by the same RE cell is an unique molecular biological phenomenon. These data illustrate the immensely important and diverse immuno-neuroendocrine functions of the thymic RE cellular network. Based on our systematic observations of the thymus in humans and other mammalian species, we suggest that the thymic RE cell network represents an extremely important cellular and humoral microenvironment in homeopathic regulatory mechanisms of the multicellular organism. Intrathymic T lymphocyte selection is a complex, multistep process, influenced by several functionally specialized RE cell subtypes and under constant immuno-neuroendocrine regulation, reflecting the dynamic changes of the organism.
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PMID:Molecular biological ontogenesis of the thymic reticulo-epithelial cell network during the organization of the cellular microenvironment. 1045 6

The thyrnus provides an optimal cellular and humoral microenvironment for the development of immunocompetent T lymphocytes. Although yolk sac derived pre-T, committed hematopoietic stem cells enter the thymus using a homing receptor, the immigration process also requires secretion of a peptide, called thymotaxin by the cells of the reticulo-epithelial (RE) network of the thymic cellular microenvironment. The thymic RE cells are functionally specialized based on their location within the thymic microenvironment. Thus, although subcapsular, cortical, and medullary RE cells are derived from a common, endodermal in origin epithelial precursor cell, their unique location within the gland causes their specialization in terms of their immunophenotypical and in situ physiological properties. The subcapsular, endocrine, RE cell layer (giant or nurse cells) is comprised of cells filled with PAS positive granules, which also express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to the medullary RE cells, these subcapsular nurse cells also produce thymosins beta 3 and beta 4. The thymic nurse cells (TNCs) display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA- DR) molecule restriction. These cells also contain transforming growth factor (TGF)-beta type II receptors and are involved in the positive selection of T cells. Transmission electronmicroscopic (TEM) observations have defined four, functional subtypes of medullary RE cells: undifferentiated squamous, villous and cystic. All subtypes were connected with desmosomes. The secreted thy nic hormones, thymulin, thymosin-alpha 1 and thymopoietin (its short form, thymopentin or TP5) were detected immunocytochemically to be produced by RE cells. Thymic RE cells also produce numerous cytokines including IL-1, IL-6, G-CSF, M-CSF, and GM-CSF molecules that likely are important in various stages of thymocyte activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion [growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), triiodothyronine (T3), somatostatin, oxytocin (OT), follicle stimulating hormone (FSH), luteinizing hormone (LH), arginine vasopressin (AVP), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRH), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), pro-enkephalin (pro-enk), and beta-endorphin (beta-end)], as well as production of a number of interleukins and growth factors and expression of receptors for all, by RE cells is an unique molecular biological phenomenon. The thymic RE cell network is most probably comprised of cells organized into sub-networks--functional units composed of RE cells with differing hormone production/hormone receptor expression profiles, involved in the various stages of T lymphocyte maturation. Furthermore, it is quite possible that even on the level of individual RE cells, the numerous projections associated with a single cell, which engulf developing lymphocytes, nurturing and guiding them in their maturation, may differ in their hormone production and/or hormone receptor expression profile, thus allowing a single cell to be involved in distinct, separate steps of the T cell maturation process. Based on our systematic observations of the thymus in humans and other mammalian species, we suggest that the thymic RE cells represent an extremely important cellular and humoral network within the thymic microenvironment and are involved in the homeopathic regulation mechanisms of the multicellular organism, in addition to the presentation of various antigens to developing lymphocytes, and providing growth regulatory signals which may range from stimulatory to apoptotic signaling within the thymus. (ABSTRACT TRUNCA
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PMID:The role of the reticulo-epithelial (RE) cell network in the immuno-neuroendocrine regulation of intrathymic lymphopoiesis. 1092 21

This issue of Peptides was inspired by a gathering of CCK researchers at the first Neuronal Cholecsytokinin Gordon Conference. The papers in this issue reflect the diversity of CCK research and demonstrate how the field has matured. Reviews describe the regulation of CCK gene expression and CCK release, the nature of the hormone binding site of the CCK A receptor, interaction of CCK, dopamine and GABA, the role of CCK in thermoregulation, sexual behavior and satiety in rodents and humans. The research articles document features of cardiovascular regulation, reduced cocaine sensitization and decreased satiety in rats that lack the CCK A receptor. Pro CCK processing in neuroblastoma cells and the elevation of CCK levels in CSF in a model of chronic pain are detailed in other articles. Three articles using different behavioral paradigms in rat and sheep examine CCK in learning and memory. Two articles that examine CCK in different behaviors that have a dopaminergic component are included. Other articles describe the interaction between a 5HT(3) antagonist and CCK-induced satiety and c-fos activation and document secretion of oxytocin and vasopressin in female patients and controls in response to CCK 4 administration. There is good reason to believe that the future is bright for research on CCK. With the organization of national and international meetings, CCK researchers have a forum for communication. Opportunities for cooperation and collaboration have never been better. The easy integration of academic basic and clinical science with industrial science bodes very well for the advancement of our understanding of the multiple roles that CCK plays in the brain and for the future development of CCK-based therapies.
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PMID:An introduction to neuronal cholecystokinin. 1145 11

Mother-reared (MR) and nursery-reared (NR) male rhesus monkeys exhibit profound and persistent differences in social and emotional behavior. Compared to MR animals, NR monkeys show reduced reciprocal social behaviors and increased agonistic behavior and high levels of stereotypy. Cerebrospinal fluid oxytocin (CSF OT) in NR monkeys was significantly reduced compared to MR monkeys measured at 18, 24, and 36 months of age. Correlations between OT and individual social behavioral profiles measured across rearing conditions also revealed a significant association between OT and the expression of affiliative social behaviors including allogrooming and reciprocal intermale mounting at each age examined. In contrast, CSF vasopressin levels did not differ according to rearing history, but did correlate with fearful behaviors independent of rearing history. Differential rearing was not associated with differences in basal or stress-related plasma cortisol, although these levels did progressively decline as monkeys matured. MR but not NR monkeys were able to use a social companion to buffer their response to a stressor, but OT levels did not appear to be sensitive to the presence of a social companion in either group. These results are consistent with earlier reports from studies of rodents suggesting an important role for central OT pathways in the development of social affiliation.
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PMID:Rearing effects on cerebrospinal fluid oxytocin concentration and social buffering in rhesus monkeys. 1270 Jul 4

Angiotensin II (50 ng/5 microl) and L-NAME (250 microg/5 microl), an inhibitor of NO synthase (NOS), were administered intracerebroventricularly alone or in combination to conscious rats. Mean arterial blood pressure (MABP) increased reaching a peak within 5 min in all groups compared to controls treated with the vehicle, artificial CSF (5 microl). MABP returned to basal levels at 30 min after angiotensin II and remained stable for the following 90 min. In animals treated with L-NAME alone, after the initial pressor response, MABP declined but began to increase progressively from 30 min until the end of the experiment at 120 min. When administered with angiotensin II, however, the initial pressor response was prolonged. Angiotensin II-induced drinking was significantly attenuated by L-NAME. In control rats, inhibiting NOS elevated plasma levels of oxytocin and vasopressin but in angiotensin II-stimulated animals, only oxytocin was further elevated after L-NAME. Thus, NO formed centrally inhibits basal secretion of oxytocin and vasopressin as well as the resting blood pressure. During stimulation with angiotensin II, NO facilitates drinking, limits the pressor response and selectively inhibits oxytocin release.
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PMID:NO and angiotensin II effects on blood pressure and fluid homeostasis. 1530 73

The detailed distribution of neural nitric oxide synthase (nNOS)-positive cerebrospinal fluid-contacting neurons (CSF-CN) was studied in the wall of the third ventricle of rats by anti-nNOS immunohistochemistry. The coexistence of nNOS and 8-arginine vasopressin (AVP) or oxytocin (OT) was also investigated in the CSF-CN using double labeling immunohistochemistry. The results demonstrated a widespread occurrence of nNOS-CSF-CN throughout the wall of the hypothalamic third ventricle. The vast majority of nNOS-CSF-CN cell bodies were of magnocellular type, commonly classified as oval, fusiform, multipolar, and inverted pear shape. These cell bodies were located in the ependyma, the subependyma, or the parenchyma, and their processes inserted in the ependymal layer or directly contacted with the CSF space. Electron microscopy demonstrated many nNOS-immunoreactive somas, dendrites, and/or axons that were situated at the subependyma, the ependyma, or the supraependyma. Generally, the distribution of OT-CSF-CN in the third ventricular wall was similar to the nNOS-CSF-CN and the ratio of NOS/OT co-expression was approximately 88%. In comparison, the distribution of AVP-CSF-CN was mainly restricted to the rostral part of the third ventricle and the ratio of nNOS/AVP co-expression was only about 6%. The widespread presence of nNOS-CSF-CN-expressing OT in the third ventricular region suggests that NO is an important messenger in the CSF-hypothalamo-hypophyseal neuroendocrine regulation that may in part act in concert with OT.
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PMID:The distribution of neural nitric oxide synthase-positive cerebrospinal fluid-contacting neurons in the third ventricular wall of male rats and coexistence with vasopressin or oxytocin. 1575 31

Galanin is a 29-amino acid peptide widely distributed in the central nervous system of vertebrates. The organization of galaninergic systems is well known in teleosts, the most advanced actinopterygians, but no data are available on primitive bony fish. To extend the evolutionary analysis of galaninergic systems we studied the distribution of galanin-like immunoreactive (GAL-ir) cells and fibers in the sturgeon brain, since chondrosteans are among the most primitive extant actinopterygians. Double-immunolabeling experiments were performed to compare the distribution of galanin with that of neurophysin, tyrosine hydroxylase, and serotonin. Numerous GAL-ir cells of cerebrospinal fluid-contacting (CSF-C) type were found in the ventral telencephalon, preoptic area, and in the tuberal and caudal hypothalamus. The distribution of GAL-ir elements in the sturgeon brain shows many similarities to that observed in other vertebrates, but also important differences, such as the abundance of GAL-ir CSF-C cells, which appear to be a primitive characteristic. GAL-ir neurons observed in the sturgeon telencephalic hemispheres perhaps represent the basic organization of common ancestors of bony fishes and tetrapods. In the preoptic-hypophyseal system, GAL-ir cells appeared to be related not only with neurophysin-expressing neurons (in the tuberal hypothalamus) but also with serotoninergic and catecholamines-synthesizing neurons (in preoptic and tuberal nuclei). Numerous GAL-ir fibers were observed in the median eminence and neural lobe of the hypophysis, indicating that galanin may play a role in the modulation of hypophyseal secretion. GAL-ir neurons were absent from the sturgeon brainstem, suggesting that their presence in other vertebrates could represent an evolutionary recent acquisition.
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PMID:Distribution of galanin-like immunoreactivity in the brain of the Siberian sturgeon (Acipenser baeri). 1586 61

Oxytocin and the nucleus accumbens have been extensively implicated in the regulation of maternal behavior, and the processing of pup-related stimuli relevant for this behavior. Oxytocin receptor density in the nucleus accumbens is highly variable in virgin female prairie voles, as is their behavioral response to pups, ranging from neglecting and infanticidal to full maternal behavior. We hypothesized that oxytocin receptor in the nucleus accumbens facilitates the expression of "spontaneous" maternal behavior in prairie voles. Forty sexually-naive adult females were exposed to pups for the first time and tested for maternal behavior. Oxytocin receptor binding in the nucleus accumbens and other brain regions was later determined using autoradiography. Females that showed maternal behavior (lick and groom the pups and hover over them for at least 30 s, n=24) had higher oxytocin receptor density in the nucleus accumbens (shell subregion) (P<0.05) than females that did not show maternal behavior or attacked the pups (n=16). No differences were found in other brain regions (medial preoptic area, septum, prelimbic cortex). In a second experiment, we tested whether infusions of the oxytocin receptor antagonist (d(CH2)5(1),Tyr(Me)2,Orn8)-AVT into the nucleus accumbens would block "spontaneous" maternal behavior. As a control region, oxytocin receptor antagonist was also infused into the caudate putamen. Ten females were infused bilaterally into the nucleus accumbens or caudate putamen with either 2 ng/0.5 microl of oxytocin receptor antagonist or CSF (vehicle). While five of 10 nucleus accumbens CSF-infused animals showed maternal behavior, none of the nucleus accumbens oxytocin receptor antagonist-infused subjects did (0/10; chi2, P<0.01). Nucleus accumbens oxytocin receptor antagonist-infused females recovered the next day and were not different from controls. Animals infused with CSF or oxytocin receptor antagonist into the caudate putamen did not differ (four/10, four/10). This is the first study to show that the nucleus accumbens is involved in the regulation of "spontaneous" maternal behavior and that oxytocin receptor in this brain region facilitates maternal responses.
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PMID:Oxytocin receptors in the nucleus accumbens facilitate "spontaneous" maternal behavior in adult female prairie voles. 1672 74

Central administration of oxytocin (OT) antagonists inhibits maternal and sexual behavior in non-primates, providing the strongest experimental evidence that endogenous OT facilitates these behaviors. While there have been a few reports that ICV administration of OT increases social behaviors in monkeys, no studies to date have assessed the effects of OT antagonists. Therefore, we studied in rhesus monkeys whether L368,899, a non-peptide antagonist produced by Merck that selectively blocks the human uterine OT receptor, penetrates the CNS after peripheral administration and alters female maternal and sexual behavior. In two studies in four male monkeys, L368,899 was injected iv (1 mg/kg) after which (1) CSF samples were collected at intervals over 4 h and (2) brains were collected at 60 min. Assay of samples confirmed that iv-administered L368,899 entered CSF and accumulated in the hypothalamus, septum, orbitofrontal cortex, amygdala and hippocampus, but not other areas. An adult female monkey was tested for interest in either an infant or sexual behavior, receiving a different iv treatment prior to each test (1 or 3 mg/kg of L368,899 or saline). OT antagonist treatment reduced or eliminated interest in the infant and sexual behavior. These results, although preliminary, are the first to directly implicate endogenous OT in activation of primate maternal interest and sexual behavior. While it remains to be empirically demonstrated that peripherally administered L368,899 blocks central OT receptors, our behavioral findings suggest that this non-peptide antagonist may facilitate testing OT involvement in a variety of social and other behaviors in primates.
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PMID:Peripherally administered non-peptide oxytocin antagonist, L368,899, accumulates in limbic brain areas: a new pharmacological tool for the study of social motivation in non-human primates. 1758 5


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