Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dynorphin-A and its related peptides are derived from prodynorphin, one of the three known endogenous opioid precursors. The prodynorphin gene is expressed in the vasopressinergic magnocellular neurons of the hypothalamus, while its peptide products are present in the vasopressin (AVP) neurosecretory vesicles of the neurohypophysis. The concentration of immunoreactive (IR) dynorphin is orders of magnitude higher in the neurohypophysis than in any other tissue, suggesting that perhaps the prodynorphin-derived peptides are secreted from the hypothalamic-neurohypophyseal unit into the general circulation. Experiments in rats have shown that osmotic stimuli increase both AVP and prodynorphin in the hypothalamus. To determine whether human hypothalamic prodynorphin is also under osmotic regulation, we measured plasma IR-dynorphin, plasma IR-AVP, and serum sodium immediately before and during the infusion of normal or hypertonic saline in normal human volunteers. Because of the unusual susceptibility of the prodynorphin-derived peptides to cleavage by endopeptidases, we also developed an appropriate plasma dynorphin extraction technique. We found that the IR-dynorphin present in human plasma was composed of 6K- and 4K-sized peptides and that no larger than 6K or smaller than 4K dynorphins were present. The infusion of normal saline did not have any significant effect on plasma IR-dynorphin, while 3% hypertonic saline increased its plasma levels. Thus, the mean IR-dynorphin level in the plasma of the volunteers infused with normal saline was 40.3 +/- 6.4 fmol/mL (mean +/- SE; n = 6) at zero time; after 30 min of infusion, plasma IR-dynorphin was 36.0 +/- 6.3, after 60 min it was 29.9 +/- 5, after 90 min it was 36.0 +/- 4.7, after 120 min it was 36.8 +/- 3.2, and after 150 min it was 36.0 +/- 6.1. The plasma IR-dynorphin level in the volunteers infused with hypertonic saline was 31.7 +/- 3.5 fmol/mL (mean +/- SE; n = 10) at zero time. After 30 min of infusion it increased to 37.4 +/- 3.8, after 60 min to 46.4 +/- 7.7, after 90 min to 56.2 +/- 9.1, after 120 min to 53.6 +/- 8.7, and after 150 min to 99.0 +/- 14.2. The increase in plasma IR-dynorphin with time was significant (P less than 0.0001) and correlated positively with serum sodium and plasma AVP. The physiological role of the prodynorphin-derived peptides of the hypothalamic-neurohypophyseal unit is not yet known.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effect of hypertonic saline infusion on the level of immunoreactive dynorphin in extracted human plasma. 197 60

The structural genes for human prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NPII; ARVP) locus and prepro-oxytocin-neurophysin-I (prepro-OT-NPI; OT) locus are closely linked separated by only 12 kilobasepairs of DNA. These two loci have been assigned to chromosome 20 by previous studies of somatic cell hybrids. We used Southern blots to analyze a restriction fragment length polymorphism detected by a probe for prepro-OT-NPI to determine the linkage relationships for the ARVP/OT loci using samples from the Centre d'Etude du Polymorphisme Humain (Paris, France) collection of families. The ARVP/OT loci demonstrated extremely close linkage with the prodynorphin (PDYN) locus, with no recombinants (theta of 0) and a log10 odds score of 5.2. Previous observations have shown the ARVP and PDYN peptides to be coexcreted in the same neurosecretory granules of some pituitary axons and that increased transcription of both genes occurs with osmotic stimulation. The combined ARVP/PT/PDYN group was also found to demonstrate linkage with other anonymous DNA segments on chromosome 20, including D20S4, D20S5, and D20S6. Using multilocus linkage analysis, the ARVP/OT loci map to the distal short arm of chromosome 20 about 15 centimorgans toward the telomere from the D20S5 locus, which is located near the middle of the short arm at 20p 12.21. These linkage relationships establish that the secretory and transcriptional associations of ARVP and PDYN extend to a close physical relationship in the human genome. Furthermore, the restriction fragment length polymorphism detected by these loci can serve as accurate markers in segregation studies of putative defects involving the OT, ARVP, or PDYN loci as well as provide a tool for studying the location of other genes, such as GH-releasing hormone.
 ...
PMID:Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin-neurophysin-I to prodynorphin and other loci on chromosome 20. 197 46

Expression of arginine-vasopressin (AVP), oxytocin (OT), dynorphin and enkephalin genes was studied with the in situ hybridization technique in embryonic rat brain serum-free cultures. Neurones were prepared from hypothalamus and extrahypothalamic structures of 16-day-old rat embryos. After 7 days in culture, AVP gene expression occurred in hypothalamic cultures only, whereas ProOT mRNAs were undetectable. By contrast, prodynorphin and proenkephalin mRNAs could be detected in both hypothalamic and extrahypothalamic cultures, however, with a higher number of cells containing proenkephalin mRNAs. These observations demonstrated that AVP, dynorphin and enkephalin, but not OT genes, can be expressed in cultures prepared from embryonic rat brain as young as 16 days old. This is the first report of an early expression of opioid peptide genes within the central nervous system suggesting that opioids could be involved in the early phases of nervous system development.
 ...
PMID:Expression of vasopressin and opiates but not of oxytocin genes studied by in situ hybridization in embryonic rat brain primary cultures. 198 Jun 42

A range of biologically different opioid peptides are synthesised as components of three distinct precursors, pro-opiomelanocortin, proenkephalin, and prodynorphin. They interact with a number of receptors which have so far been characterised as mu, delta, kappa, sigma, and epsilon. It is unclear which ligands bind to which receptors under physiological circumstances, but preferential in vitro interactions include enkephalins with delta receptors, dynorphin with kappa receptors, and beta-endorphin with epsilon receptors. Post-translational processing determines which of several opioid products are produced from each precursor, but the identity of the enzymes involved and regulation of processing is unknown. Opioid involvement in the neuroendocrine and cardiovascular systems is reviewed. Naloxone-sensitive opioid mechanisms are implicated in the control of gonadotrophin and adrenocorticotropic hormone secretion and in the hypotension of various types of shock. The investigation of possible dynorphin involvement in neurohypophysial function is taking place because vasopressin and dynorphin A (1-8) have been shown to coexist in the neurosecretory vesicles of magnocellular neurons.
 ...
PMID:Opioid biology: the next set of questions. 286 Aug 88

Peptides derived from prodynorphin and provasopressin precursors coexist within neurosecretory vesicles of magnocellular neurons of the rat hypothalamus projecting to the posterior pituitary. The secretory activity of these neurons can be stimulated with physiological manipulations that elevate plasma levels of vasopressin (VP), such as dehydration and salt-loading. Evidence indicates that both VP- and prodynorphin-derived peptides are secreted under such conditions. With chronic osmotic challenge, the mRNAs for both prodynorphin and provasopressin increase in parallel in the supraoptic and paraventricular nuclei of the hypothalamus, and not within nonmagnocellular cell groups projecting elsewhere in the brain. The results indicate an example of coordinate regulation of mRNA expression for coexisting peptides within the brain. These results from microdissected tissues have been coupled with the more anatomically precise method of in situ hybridization histochemistry. Using 35S-radiolabeled synthetic oligonucleotides complementary to VP and dynorphin mRNAs, these mRNAs have been autoradiographically localized to magnocellular parikarya in the rat hypothalamus. Results also indicate that this technology can be used for regulatory studies, as evidenced by the increased hybridization of VP oligonucleotide to hypothalamic nuclei from salt-loaded rats.
 ...
PMID:Hypothalamic dynorphin and vasopressin mRNA expression in normal and Brattleboro rats. 287 54

Opioid peptides derived from the precursor, prodynorphin, are co-localized with vasopressin in the hypothalamus and posterior pituitary, and vasopressin and prodynorphin synthesis are coordinately regulated during salt-loading. We had previously found that chronic ethanol ingestion resulted in decreased levels of hypothalamic and extrahypothalamic vasopressin mRNA, and the current study investigated the effect of ethanol ingestion on prodynorphin mRNA levels. A cRNA probe was constructed from a PCR product amplified from mouse genomic DNA. Cloning and sequencing of the PCR product revealed that the sequence of the mouse prodynorphin gene used to synthesize the probe is highly conserved, with high sequence similarity to corresponding regions of the gene in other mammalian species. In situ hybridization using the cRNA probe showed a widespread distribution of prodynorphin mRNA in mouse brain. In dehydrated mice, prodynorphin mRNA was significantly increased in the hypothalamus and nearly all other brain areas examined. In ethanol-fed mice, prodynorphin mRNA was also significantly increased in hypothalamus (50-60%) and in most brain areas. In the same mice, measurement of hypothalamic vasopressin mRNA confirmed a significant (approximately 60%) decrease. These results indicate that hypothalamic vasopressin and prodynorphin mRNA can be differentially regulated in certain situations.
 ...
PMID:Prodynorphin and vasopressin mRNA levels are differentially affected by chronic ethanol ingestion in the mouse. 825 70

Vasopressin and oxytocin mRNAs, which are normally translated in the perikarya of magnocellular neurons, have recently been demonstrated to be also present in axons and nerve terminals which are located in the posterior pituitary. The physiological significance of this observation has not yet been resolved. In order to gain further insight into the function and plasticity of the peptidergic neuron the question was addressed whether axonal localization is a unique feature of the above-mentioned transcripts. Biochemical evidence is presented that magnocellular axons and nerve terminals also contain mRNA species encoding a member of the neurofilament protein family and the prodynorphin precursor. These data imply that axons may harbour a variety of additional protein-encoding transcripts. Furthermore, it is shown that in the mutant (Brattleboro) rat, which lacks detectable levels of vasopressin but which still transcribes the corresponding gene, axonal vasopressin but not oxytocin mRNA contents are dramatically reduced. Most likely, vasopressin transcripts are absent from the nerve terminals as a consequence of the impaired precursor biosynthesis in the cytoplasm of the mutant rat.
 ...
PMID:Diversity of mRNAs in the Axonal Compartment of Peptidergic Neurons in the Rat. 1210 10

Dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland to reduce water loss in the urine. Vasopressin secretion is determined by action potential firing in vasopressin neurones, which can exhibit continuous, phasic (alternating periods of activity and silence), or irregular activity. Autocrine kappa-opioid inhibition contributes to the generation of activity patterning of vasopressin neurones under basal conditions and so we used in vivo extracellular single unit recording to test the hypothesis that changes in autocrine kappa-opioid inhibition drive changes in activity patterning of vasopressin neurones during dehydration. Dehydration increased the firing rate of rat vasopressin neurones displaying continuous activity (from 7.1 +/- 0.5 to 9.0 +/- 0.6 spikes s(1)) and phasic activity (from 4.2 +/- 0.7 to 7.8 +/- 0.9 spikes s(1)), but not those displaying irregular activity. The dehydration-induced increase in phasic activity was via an increase in intraburst firing rate. The selective -opioid receptor antagonist nor-binaltorphimine increased the firing rate of phasic neurones in non-dehydrated rats (from 3.4 +/- 0.8 to 5.3 +/- 0.6 spikes s(1)) and dehydrated rats (from 6.4 +/- 0.5 to 9.1 +/- 1.2 spikes s(1)), indicating that kappa-opioid feedback inhibition of phasic bursts is maintained during dehydration. In a separate series of experiments, prodynorphin mRNA expression was increased in vasopressin neurones of hyperosmotic rats, compared to hypo-osmotic rats. Hence, it appears that dynorphin expression in vasopressin neurones undergoes dynamic changes in proportion to the required secretion of vasopressin so that, even under stimulated conditions, autocrine feedback inhibition of vasopressin neurones prevents over-excitation.
 ...
PMID:Dehydration-induced modulation of kappa-opioid inhibition of vasopressin neurone activity. 1982 41

Activation of melanocortin-4 receptors (MC4Rs) restrains feeding and prevents obesity; however, the identity, location, and axonal projections of the neurons bearing MC4Rs that control feeding remain unknown. Reexpression of MC4Rs on single-minded 1 (SIM1)(+) neurons in mice otherwise lacking MC4Rs is sufficient to abolish hyperphagia. Thus, MC4Rs on SIM1(+) neurons, possibly in the paraventricular hypothalamus (PVH) and/or amygdala, regulate food intake. It is unknown, however, whether they are also necessary, a distinction required for excluding redundant sites of action. Hence, the location and nature of obesity-preventing MC4R-expressing neurons are unknown. Here, by deleting and reexpressing MC4Rs from cre-expressing neurons, establishing both necessity and sufficiency, we demonstrate that the MC4R-expressing neurons regulating feeding are SIM1(+), located in the PVH, glutamatergic and not GABAergic, and do not express oxytocin, corticotropin-releasing hormone, vasopressin, or prodynorphin. Importantly, these excitatory MC4R-expressing PVH neurons are synaptically connected to neurons in the parabrachial nucleus, which relays visceral information to the forebrain. This suggests a basis for the feeding-regulating effects of MC4Rs.
...
PMID:MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. 2515 44