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)

Agents previously implicated in control of the hypothalamo-pituitary-gonadal axis were screened for their ability to regulate male rat gonadotropes directly. GnRH-evoked gonadotropin release is accompanied by oscillations of intracellular Ca2+ concentration ([Ca2+]i) and of an outward K+ current that is activated by Ca2+. Substances that caused current responses similar to those with GnRH were hypothesized to evoke secretion. Endothelin-1, oxytocin, neurotensin, pituitary adenylate cyclase-activating polypeptide, and serotonin raised [Ca2+]i and evoked LH release as assayed by the reverse hemolytic plaque assay. These agents affected only subpopulations of gonadotropes establishing functional heterogeneity of pituitary gonadotropes. One neuromodulator (ATP) evoked ionic current in all gonadotropes but the current was different than that evoked by GnRH. Many other substances, including galanin and neuropeptide Y, caused no changes in currents and were considered not to affect [Ca2+]i and not to be secretagogues for gonadotropes.
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PMID:Functional heterogeneity of pituitary gonadotropes in response to a variety of neuromodulators. 896 Dec 53

We examined the expression of regulated endocrine-specific protein of 18-kD (RESP18) in selected peptidergic and catecholaminergic neurons of adult rat brain. In the hypothalamic paraventricular, supraoptic, and accessory nuclei, RESP18 mRNA was highly expressed in neurons immunostained for oxytocin and vasopressin. RESP18 mRNA was also highly expressed in paraventricular nucleus neurons immunostained for corticotropin-releasing hormone, thyrotropin-releasing hormone, and somatostatin. RESP18 mRNA was expressed in POMC cells of the arcuate nucleus, in neuropeptide Y cells of the dorsal tegmental nucleus, lateral reticular nucleus, and hippocampus, and in brainstem catecholaminergic neurons. RESP18 mRNA expression was high in all paraventricular and arcuate neurons, but RESP18 protein was detectable in the perikarya of a subset of these neurons, suggesting an important post-transcriptional component to the regulation of RESP18 expression. RESP18 antisera immunostained perikarya but not axon fibers or terminals. Sub-cellular fractionation of homogenates of several hypothalamic nuclei identified RESP18 protein in fractions enriched in endoplasmic reticulum. The presence of 22- and 24-kD RESP18 isoforms in the neural lobe of the pituitary indicated that some RESP18 protein exited the endoplasmic reticulum. The post-transcriptional regulation of RESP18 expression and localization of RESP18 protein primarily to the endoplasmic reticulum suggests that RESP18 plays a regulatory role in peptidergic neurons.
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PMID:Expression of RESP18 in peptidergic and catecholaminergic neurons. 928 14

The adipose tissue-derived hormone leptin regulates body weight homeostasis by decreasing food intake and increasing energy expenditure. The weight-reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor (LR) in the hypothalamus. We have used immunohistochemistry to localize LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum against a portion of the intracellular domain of LR that is common to all LR isoforms. The antiserum recognized the short and long isoforms of LR in transfected hematopoietic BaF3 cells. To examine the chemical nature of target cells for leptin, direct double-labeling immunofluorescence histochemistry was applied. The results show extensive distribution of LR-like immunoreactivity (LR-LI) in the brain with positively stained cells present, e.g., in the choroid plexus, cerebral cortex, hippocampus, thalamus, and hypothalamus. In the hypothalamus, strongly LR-IR neurons were present in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), periventricular nucleus, arcuate nucleus, and lateral hypothalamus. Weaker LR-IR neurons were also demonstrated in the lateral and medial preoptic nuclei, suprachiasmatic nucleus, ventromedial and dorsomedial nuclei, and tuberomammillary nucleus. Confocal laser scanning microscopy showed LR-LI in the periphery of individual cells. In magnocellular neurons of the SON and PVN, LR-LI was demonstrated in vasopressin- and oxytocin-containing neurons. In parvocellular neurons of the PVN, LR-LI was demonstrated in many corticotropin-releasing hormone-containing neurons. LR-IR neurons were mainly seen in the ventromedial aspect of the arcuate nucleus, where LR-LI co-localized with neuropeptide Y. In the ventrolateral part of the arcuate nucleus, LR-LI was present in many large adrenocorticotropic hormone-IR proopiomelanocortin-containing neurons and in a few galanin-, neurotensin-, and growth hormone-releasing hormone-containing neurons. In the dorsomedial arcuate nucleus, few tyrosine hydroxylase (dopamine)-containing neurons were seen to have LR-LI. Melanin-concentrating hormone-containing neurons in the lateral hypothalamus had LR-LI. Based on the immunohistochemical results, possible interactions of leptin with brain mechanisms are discussed.
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PMID:Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. 941 31

Neuropeptide Y and peptide YY are important central and peripheral modulators of cardiovascular and neuroendocrine functions, that act through multiple receptor subtypes, Y1 through Y5. A neuropeptide Y-binding site of the Y2 type was characterized by ligand-binding studies in isolated nerve terminals from the rat neurohypophysis. Functionally, neuropeptide Y and peptide YY dose-dependently triggered arginine 8-vasopressin and oxytocin release from perfused isolated terminals, and potentiated the arginine-8-vasopressin release induced by depolarization. Osmotic stimulation by salt loading of rats for two and seven days caused a more than three-fold increase in the neuropeptide Y content of the nerve endings. However, the Y2 receptor expression and arginine-8-vasopressin content declined, showing that the neuropeptide Y system is dynamic and suggesting that it plays a physiological role in salt and water homeostasis. Two sets of observations suggest the arginine-8-vasopressin release by neuropeptide Y may not be explained by neuropeptide Y effects on intracellular Ca2+. First, absence of Ca2+ from the perfusion medium did not affect the arginine-8-vasopressin release, and secondly neuropeptide Y did not change intraterminal Ca2+ concentrations. Pretreatment with pertussis toxin blocked arginine-8-vasopressin secretion by neuropeptide Y, suggesting activation of Gi or Go heterotrimeric G-proteins are required for secretion. It is concluded, that the nerve endings of the neurohypophysis contain a complete neuropeptide Y system with ligand and receptors. Neuropeptide Y may act in an autocrine fashion via activation of Y2 neuropeptide Y receptors to stimulate the release of vasopressin and oxytocin via a Gi/Go dependent secretory mechanism.
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PMID:Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release. 948 7

Examination of neuropeptide families can provide information about phyletic relationships and evolutionary processes. In this article the oxytocin/vasopressin family, growth hormone releasing factor (GRF) superfamily and the substance P/tachykinin family have been considered in detail because they have been isolated from an extraordinarily diverse array of species from several vertebrate classes and invertebrate phyla. More important is that the nucleotide sequence of mRNA or cDNA encoding many of these peptides has been determined, which has allowed evolutionary distances to be estimated based on the DNA mutation rate. The origin of a given family lies in a primordial gene that arose many millions of years ago, and through time, exon duplication and insertion, gene duplication, point mutation and exon loss, the family developed into the forms that are now recognised. For example, in birds, GRF and pituitary adenylate cyclase activating peptide (PACAP) are encoded by the same gene, which probably arose as a result of exon duplication and tandem insertion of the ancestral GRF gene. In mammals GRF is the sole product on one gene, and PACAP is the product of a gene that also produces PACAP-related peptide (PRP), which is homologous to GRF. Thus it appears that between birds and mammals the GRF/PACAP gene duplicated: exon loss gave rise to the mammalian GRF gene, while mutation led to the formation of the mammalian PRP/PACAP gene. The neuropeptide Y superfamily is considered briefly, as is cionin, which is an invertebrate peptide that is closely related to the mammalian gastrin/cholecystokinin family.
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PMID:Neuropeptide families: evolutionary perspectives. 953 70

Mammalian pineal gland receives peptidergic (e.g., vasoactive intestinal peptide [VIP]; peptide histidine isoleucine [PHI]; neuropeptide Y, NPY; substance P, calcitonin gene-related peptide [CGRP], arginine vasopressin [AVP] and oxytocin [OXT]) fibers in addition to sympathetic innervation. The dynamics of cAMP efflux and melatonin (MT) secretion were compared during the infusion of these peptides in our long-term perifusion system. VIP and PHI enhanced both pineal cAMP efflux and MT secretion in a dose-dependent manner (10 nM to 10 microM). However, the potency of PHI was slightly less. The peak of cAMP release always precedes that of MT production. The possible interactions between adrenergic and peptidergic compounds in the regulation of pineal cAMP efflux and MT secretion were also studied. VIP acts on specific peptidergic receptors, since its stimulatory effect could only be reduced by a VIP receptor antagonist. VIP has an additive effect at a lower (100 nM) concentration combined with norepinephrine (NE). NPY (100 nM) can completely block NE-induced MT secretion, but the decrease in cAMP efflux is less. However, NPY does not significantly influence VIP-stimulated cAMP efflux or MT secretion. These data suggest that NE, VIP, and NPY are differently involved in the cAMP and calcium signaling. The other neuropeptides are ineffective.
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PMID:Adrenergic and peptidergic control of the regulation of cAMP efflux and melatonin secretion from perifused rat pineal gland. 979 35

1. Sigma receptors bind a diverse group of chemically unrelated ligands, including pentazocine, apomorphine (a dopamine receptor agonist) and haloperidol (a dopamine receptor antagonist). Although sigma binding sites are widely distributed, their physiological roles are poorly understood. Here, the whole-terminal patch-clamp technique was used to demonstrate that sigma receptors modulate K+ channels in rodent neurohypophysis. 2. Previous work suggested that dopamine type 4 (D4) receptors modulate neurohypophysial K+ current, so this study initially tested the role of dopamine receptors. Experiments using transgenic mice lacking D2, D3 or D4 receptors indicated that the reduction of K+ current by PPHT and U101958 (ligands thought to be selective for dopamine receptors) is not mediated by dopamine receptors. The sensitivity of the response to U101958 (a drug that binds to D4 receptors) was the same in both wild-type and D4 receptor-deficient mice. 3. Experiments with other ligands revealed a pharmacological signature inconsistent with any known dopamine receptor. Furthermore, dopamine itself (at 100 microM) had no effect. Thus, despite the activity of a number of putative dopamine receptor ligands, dopamine receptors play no role in the modulation of neurohypophysial K+ channels. 4. Because of the negative results regarding dopamine receptors, and because some of the dopamine receptors ligands used here are known to bind also to sigma receptors, experiments were conducted to test for the involvement of sigma receptors. In rat neurohypophysis the sigma receptor ligands SKF10047, pentazocine, and ditolylguanidine all reversibly inhibited K+ current in a concentration-dependent fashion, as did haloperidol and apomorphine (ligands that bind to both dopamine and sigma receptors). The activity of these and other ligands tested here matches the reported binding specificity for sigma receptors. 5. Fifteen candidate endogenous sigma receptor ligands, including biogenic amines (e.g dopamine and serotonin), steroids (e.g. progesterone), and peptides (e.g. neuropeptide Y), were screened for activity at the sigma receptor. All were without effect. 6. Haloperidol reduced K+ current proportionally at all voltages without shifting the voltage dependence of activation and inactivation. Sigma receptor ligands inhibited current through two distinct K+ channels, the A-channel and the Ca2+-dependent K+ channel. In rat, all drugs reduced current through both channels proportionally, suggesting that both channels are modulated by a single population of sigma receptors. In contrast, mouse peptidergic nerve terminals either have two receptors which are sensitive to these drugs, or a single receptor that is differentially coupled to ion channel function. 7. The inhibition of voltage-activated K+ current by sigma receptors would be expected to enhance the secretion of oxytocin and vasopressin from the neurohypophysis.
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PMID:K+ channel modulation in rodent neurohypophysial nerve terminals by sigma receptors and not by dopamine receptors. 1033 90

Animal experiments have already shown that neurotransmitters and neuropeptides are not only important for normal functioning of the adult central nervous system (CNS) but are also crucial to its development. However, information on the spatio-temporal distribution of these endogenous substances in the developing human CNS is still scarce. With the use of immunocytochemical staining and a constant supply of properly fixed human abortuses from southern China, an early appearance of acetylcholinesterase, enkephalin, and substance P immunoreactivities was detected first in the spinal cord (weeks 5 to 7 of gestation), then in the brainstem nuclei (weeks 11 to 12). Their overlapping localizations in many regions of the CNS suggest possible interactions among neurons containing these substances, which are in turn important for the proper establishment of the neuronal circuitry. Immunoreactivity for neuropeptide Y appeared initially in the lateral region of upper segments of the spinal cord at week 12 of gestation, then spread latero-medially and cranio-caudally to the sacral region. In the hippocampus, neuropeptide Y neurons appeared from week 15 onwards. Serotoninergic neurons were found in the dorsal raphe nucleus at week 10 and then decreased in number as the fetus grew older. Somatostatin releasing inhibitory factor, vasopressin, and oxytocin were detected in the hypothalamus from weeks 12 to 14 onwards, and monoamine oxidase, succinic dehydrogenase, parvalbumin, calbindin D28K, and vasoactive intestinal peptide were found in the visual cortex at midgestation. The early appearance and the abundance of the neurotransmitters and neuropeptides in the developing CNS indicate that they may play a key role in neuronal differentiation.
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PMID:Early appearance of acetylcholinergic, serotoninergic, and peptidergic neurons and fibers in the developing human central nervous system. 1040 66

Distinct brain peptidergic circuits govern peripheral energy homeostasis and related behavior. Here we report that mitochondrial uncoupling protein 2 (UCP2) is expressed discretely in neurons involved in homeostatic regulation. UCP2 protein was associated with the mitochondria of neurons, predominantly in axons and axon terminals. UCP2-producing neurons were found to be the targets of peripheral hormones, including leptin and gonadal steroids, and the presence of UCP2 protein in axonal processes predicted increased local brain mitochondrial uncoupling activity and heat production. In the hypothalamus, perikarya producing corticotropin-releasing factor, vasopressin, oxytocin, and neuropeptide Y also expressed UCP2. Furthermore, axon terminals containing UCP2 innervated diverse hypothalamic neuronal populations. These cells included those producing orexin, melanin-concentrating hormone, and luteinizing hormone-releasing hormone. When c-fos-expressing cells were analyzed in the basal brain after either fasting or cold exposure, it was found that all activated neurons received a robust UCP2 input on their perikarya and proximal dendrites. Thus, our data suggest the novel concept that heat produced by axonal UCP2 modulates neurotransmission in homeostatic centers, thereby coordinating the activity of those brain circuits that regulate daily energy balance and related autonomic and endocrine processes.
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PMID:Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers. 1057 39

Cocaine and amphetamine regulated transcript (CART) has been identified as one of the most abundant mRNAs in the rat hypothalamus. The objective of the present study was to elucidate the distribution of CART peptide immunoreactive (CARTir) neurons in the monkey hypothalamus and characterize their ultrastructural features and synaptic connections in the paraventricular nucleus (PVN). CARTir neurons were particularly abundant in the PVN, supraoptic nucleus (SON), infundibular nucleus, and premammillary nucleus, whereas the anterior, lateral, and posterior hypothalamic areas as well as the posterior nucleus displayed moderate immunoreactivity. Dense bundles of CARTir fibers exited the PVN and SON and followed a trajectory to the infundibulum similar to that previously shown for vasopressin and oxytocin fibers. The posterior pituitary was densely packed with large CARTir varicosities which, in some cases, were apposed to labeled pituicytes. The external/palisade zone of the median eminence contained rich plexuses of small CARTir varicose fibers, and the internal/fibrous zone was enriched in large axon-like processes. Electron microscope analysis of the PVN revealed (1) that CART peptide immunoreactivity is found in neurosecretory and non-neurosecretory neurons contacted predominantly by unlabelled terminals forming asymmetric synapses, (2) that CARTir terminals resemble glutamatergic and/or noradrenergic boutons and form asymmetric synapses with non-neurosecretory dendrites, and (3) that neuropeptide Y (NPY)-containing terminals are apposed to CARTir neurons in the medial part of the nucleus. In conclusion, our findings demonstrate that CART peptide is abundant in neuronal perikarya and axon terminals throughout the monkey hypothalamus and along the hypothalamopituitary axis. This strengthens the idea that CART peptides may act as putative neurotansmitters/neuromodulators that mediate various neuroendocrine and autonomic functions in primates.
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PMID:CART peptide immunoreactivity in the hypothalamus and pituitary in monkeys: analysis of ultrastructural features and synaptic connections in the paraventricular nucleus. 1060 89


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