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

Using sensitive specific RIAs for vasopressin (AVP) and the two major human neurophysins, the relationship between AVP and the individual human neurophysins was investigated in man by measuring changes in plasma concentrations in physiological and pathological states known to be associated with changes in AVP secretion. Dehydration, water loading, and hemorrhage produced small but significant changes in plasma AVP concentrations without changes in the individual human neurophysins. In response to the stimulus of cigarette smoke inhalation, large parallel changes in plasma AVP and human neurophysin I (HNPI) levels were seen without change in plasma human neurophysin II (HNPII) levels. In the pathological states of diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion,the observations more strongly supported a specific association between AVP and NHPI. In eight patients with central diabetes insipidus, plasma AVP and HNPI levels were low or undetectable, while plasma HNPII levels were normal. There was a clear distinction of both plasma AVP and HNPI levels in patients with central diabetes insipidus and those in patients whti nephrogenic diabetes insipidus. In 14 patients with the syndrome of inappropriate antidiuretic hormone secretion due to causes other than ectopic AVP production from tumors, plasma AVP and HNPI levels were elevated or normal, while plasma HNPII levels were normal. There was a highly significant positive correlation (r = 0.99) between plasma AVP and HNPI levels in these patients, with a 1:1 molar ratio. These data suggest that the secretion of AVP and HNPI in man are functionally related, while the secretion of HNPII is independent of AVP secretion.
 ...
PMID:Plasma vasopressin and human neurophysins in physiological and pathological states associated with changes in vasopressin secretion. 47 48

The gene responsible for familial vasopressin-resistant nephrogenic diabetes insipidus (NDI) has been localized to a small region of the human X-chromosome (Xq28). A series of hamster lung fibroblast and mouse lymphocyte cell lines carrying fragments of the wild type human X-chromosome was analyzed for vasopressin renal-type V2 receptor expression, to test the hypothesis that the NDI locus may have identity with the V2 receptor gene. V2 receptor binding activity and induction of cAMP production in response to [Arg8] vasopressin (AVP) were exhibited by all cell lines carrying the wild type NDI locus, in contrast to control cell lines. AVP stimulation of cAMP production was concentration-dependent and could be almost completely inhibited by co-incubation with a V2-V1 receptor-specific antagonist. The V2-specific agonist [Mpa1,Val4,Sar7]AVP was as potent as AVP in inducing cAMP production by NDI-DNA-carrying cells, whereas no response was shown to other hormones such as calcitonin, oxytocin (less than 10(-8) M), isoproterenol, or an oxytocin-specific agonist. All results were consistent with the hypothesis that the V2 receptor gene co-localized with the NDI locus, supporting the view that the loci are one and the same.
 ...
PMID:Derivatives of somatic cell hybrids which carry the human gene locus for nephrogenic diabetes insipidus (NDI) express functional vasopressin renal V2-type receptors. 216 11

Acetylcholinesterase activity was demonstrated histochemically at light- and electron-microscopic levels, in Vibratome sections of the supraoptic nucleus of fixed hypothalami derived from osmotically stimulated and unstimulated Long Evans rats, from homozygous Brattleboro rats with hypothalamic diabetes insipidus, from lactating rats, from normal adult male house mice (Mus musculus) and from mice with hereditary nephrogenic diabetes insipidus (di/di). Reaction product was located in supraoptic magnocellular neurons; in dorsal and rostral aspects of the supraoptic nuclei lightly stained cells predominate, whereas in ventral and caudal regions densely staining perikarya predominate. Pre- and post-embedding immunocytochemical detection of oxytocin-neurophysin or vasopressin-neurophysin, combined with acetylcholinesterase histochemistry, showed that the lightly staining cells are oxytocinergic, and the densely staining cells vasopressinergic. Osmotic stimulation of the animals, either by substitution of drinking water for 3 days with 2.5% saline or reason of genetic defects which result in diabetes insipidus, enhanced the acetylcholinesterase activity of the vasopressin neurons but had little effect on the weekly acetylcholinesterase-reactive oxytocin cells. Acetylcholinesterase activity was particularly marked in the hypertrophied abnormal magnocellular neurons of homozygous Brattleboro rats which do not release significant amounts of vasopressin. The increased acetylcholinesterase activity in osmotically stimulated animals cannot, therefore, be a function of vasopressin. Acetylcholinesterase activity was also detected in large multipolar neurons lying dorsolateral to the supraoptic nucleus, and in their fine axonal processes which project towards the supraoptic nucleus. A very few synaptic boutons surrounded by acetylcholinesterase reaction product were found in contact with magnocellular neuron basal dendrites. However, much of the punctate acetylcholinesterase reactivity observed at the light microscopic level and previously interpreted as representing the loci of cholinergic synaptic boutons was shown to be intracellular, and probably caused by acetylcholinesterase activity in some large, secondary lysosomes.
 ...
PMID:Differential distribution of acetylcholinesterase activity among vasopressin- and oxytocin-containing supraoptic magnocellular neurons. 276 86

Arginine vasopressin (AVP) is a potent neuroactive and vasoactive nonapeptide encoded in and processed from a precursor, preproarginine vasopressin-neuro-physin II (preproAVP-NPII). To study the physiologic consequences of a genetic model of chronic hypervasopressinemia transgenic mice were produced by introduction of a mouse metallothionein-rat-ppAVP-NPII fusion gene into the germ line of mice. Three stable transgenic pedigrees were analyzed through several generations. Levels of immunoreactive AVP and neurophysin (NP) in sera, livers, kidneys, intestines, pancreas, and brains were markedly elevated. Chromatographic analyses showed sera levels of approximately 500 pg/ml (normal 0-20 pg/ml) of authentic AVP non-apeptide and serum osmolalities were elevated, 315.4 +/- 1.4 mosm/liter (control, 307.3 +/- 1.1), consistent with a state of mild nephrogenic diabetes insipidus. Brain levels of immunoreactive AVP in transgenic mice were 3-4-fold elevated 145 +/- 15 ng/g versus 31 +/- 7 (controls). Although immunoreactive AVP in livers and intestines, and to some extent kidneys, consisted predominantly of unprocessed precursors, in brain and pancreas greater than 90% of AVP consisted of processed bioactive nonapeptide, as determined by chromatography and measurements of cAMP-generation in LLC-PK1 cells. Immunocytochemistry localized immunoreactive AVP to the exocrine pancreas and to the magnacellular neurons (SON and PVN) of the hypothalamus. Expression of the fusion gene in the hypothalamus was further demonstrated by Northern analyses of fusion gene specific transcripts and in situ histohybridization. Although the fusion gene contained only 35 base pairs of 5'-flanking DNA of the ppAVP-NPII gene, a tentative neuronal cell-specific expression element, -17GCCCAG-CC-10 resides in this sequence and may confer neuron-specific expression to the fusion gene.
 ...
PMID:Metallothionein-vasopressin fusion gene expression in transgenic mice. Nephrogenic diabetes insipidus and brain transcripts localized to magnocellular neurons. 280 95

Two neurophysins (NPs) that are thought to be the primary protein forms produced with the hormones vasopressin (VP) and oxytocin (OT) were isolated from 5000 human pituitary glands. In sucrose gradient centrifugation of human neural lobes, each of these NPs had a distribution similar to that of either VP or OT. Such differential localization of 1 human NP (HNP) with VP and the other HNP with OT suggests an association of their biosynthesis, and it is on the basis of this association that 1 NP has been named VP-associated HNP (VP-HNP) and the other OT-associated HNP (OT-HNP). The purified proteins were complexed to bovine thyroglobulin in order to develop specific antisera. RIAs developed with these antisera are effective for each HNP in the range of 5-320 pg. Reference standards in both assays were corrected for protein content using amino acid analysis to obtain absolute protein concentration; this type of correction is recommended for all RIAs that measure proteins. The RIAs were used to measure the concentrations of HNPs in unextracted human plasma. In healthy, sitting, normally hydrated subjects of both sexes, VP-HNP and OT-HNP were, respectively, 73 +/- 5 and 382 +/- 30 pg/ml (mean +/- SEM; n = 20); there was no significant difference between values in males and females, provided the latter were not taking medication. Women on oral contraceptives had elevated (> 3 times normal) levels of OT-HNP but normal levels of VP-HNP. Eleven patients who had the syndrome of inappropriate secretion of antidiuretic hormone had elevated levels of VP-HNP but not necessarily of OT-HNP. Surgery was found to consistently increase plasma VP-HNP but not OT-HNP. In two of six subjects smoking caused a dramatic release of VP-HNP, as indexed by plasma levels which rose to more than 50 times the control values. One patient with lithium-induced nephrogenic diabetes insipidus had elevated plasma concentrations of both NPs. The sensitivity and specificity of the RIAs may make them useful clinically in certain pathological states.
 ...
PMID:Isolation and partial characterization of two human neurophysins: their use in the development of specific radioimmunoassays. 741 70

The molecular cloning and characterization of receptors for [Arg8] vasopressin and oxytocin were recently accomplished. These receptors form a subfamily among the large number of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors with seven transmembrane domains. The molecular cloning of the human V2 receptor was rapidly followed by the identification of mutations in the V2 receptor gene segregating with the clinical phenotype in families with X-linked nephrogenic diabetes insipidus. These naturally occurring mutations will be useful to identify critical functional regions of the vasopressin V2 receptor. Carrier detection and early diagnosis of affected male infants are available and can avert the physical and mental retardation that are the consequences of episodes of dehydration. Together with the recent cloning of the vasopressin-regulated water channels in the apical membrane of the collecting tubule, these developments will enable direct investigation of the mammalian concentrating mechanism.
 ...
PMID:Molecular and cellular biology of vasopressin and oxytocin receptors and action in the kidney. 785 Apr 11

Constitutive nitric oxide synthase (cNOS) was immunolocalized to study its role in osmotic regulation. Immunoreactivity was observed in all major hypothalamic osmoregulatory structures, the organum vasculosum laminae terminalis, subfornical organ, median preoptic nucleus, and supraoptic and paraventricular nuclei. These nuclei were compared in normal Long-Evans rats and homozygous Brattleboro rats with hereditary hypothalamic diabetes insipidus and in normal mice and mice with hereditary nephrogenic diabetes insipidus. About 50% of supraoptic neurons in Long-Evans rats and 90% in Brattleboro rats were cNOS immunopositive; a qualitatively similar difference occurred in the paraventricular nucleus. Mice with hereditary nephrogenic diabetes insipidus also showed a greater proportion of cNOS-positive supraoptic neurons (50%) than normal mice (20%). However, the number of cNOS-positive cells in the organum vasculosum laminae terminalis, subfornical organ, and median preoptic nucleus dis not differ significantly between diabetic and normal animals. The similar changes in cNOS in two mutant strains in which the only common feature is chronic osmotic stimulation shows that differences in vasopressin and oxytocin are not involved in the regulation of cNOS. The results suggest strongly that cNOS is involved in long term modulation of the hypothalamo-neurohypophysial system and, hence, body water and electrolyte homeostasis, and that cNOS is itself regulated by body osmotic status.
 ...
PMID:Constitutive nitric oxide synthase in hypothalami of normal and hereditary diabetes insipidus rats and mice: role of nitric oxide in osmotic regulation and its mechanism. 861 10

The oxytocin and the vasopressin V1a, V1b and V2 receptors have recently been cloned and shown to form a sub-family within the large superfamily of G-protein-linked receptors. Renal V2 receptors mediate vasopressin-induced water reabsorption via induction of intracellular cAMP production in collecting duct cells. Most remaining actions of vasopressin on blood vessel constriction, liver glycogenolysis, platelet adhesion, adrenal angiotensin II secretion and certain brain functions are mediated via v1a-type receptors that are coupled to a Gq/11 protein. V1 receptor activation leads to stimulation of phospholipases C, D and A2 and an increase in intracellular calcium. Vasopressin stimulates pituitary corticotrophin release via a third vasopressin receptor type (V1b) which is present on corticotrophs. Oxytocin induces myometrial contraction, endometrial prostaglandin F2 alpha production, mammary gland milk ejection, renal natriuresis and specific sexual, affiliative and maternal behaviours via oxytocin receptors which are also coupled to a Gq/11 protein. Although only one oxytocin receptor type has been cloned so far, recent binding studies indicate that uterine endometrial oxytocin receptors may constitute a distinct receptor subtype. In contrast to most other membrane receptors, the expression of oxytocin receptors undergoes very rapid and physiologically relevant up-and-down-regulation. A > 100-fold up-regulation of uterine oxytocin receptors occurs during gestation and may represent the trigger for parturition. Indeed, oxytocin receptor antagonists are able to counteract preterm labour and may soon be available for clinical use. The presence of oxytocin receptors on breast cancer cells and the growth-inhibitory effects of OT suggest a potential use of oxytocin analogues for breast cancer treatment. Whereas no mutations of the oxytocin or V1a or V1b receptors have been found, over 60 different genetic mutations of the (renal) V2 receptor have been described which represent the cause for congenital nephrogenic diabetes insipidus.
 ...
PMID:Vasopressin and oxytocin receptors. 873 52

The molecular cloning and characterization of receptors for the nonapeptide hormone family vasopressin-oxytocin was rapidly followed by the identification of mutations in the V2 receptor gene segregating with the clinical phenotype in more than a hundred families with X-linked nephrogenic diabetes insipidus. Together with the recent cloning of the vasopressin-regulated water channel in the apical membrane of the collecting duct tubule and of the identification of rare autosomal recessive nephrogenic diabetes insipidus patients with mutations in the AQP2 gene, these developments enable carrier detection and early diagnosis of infants with congenital nephrogenic diabetes insipidus.
 ...
PMID:Vasopressin receptors in health and disease. 874 82