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)

Pro-vasopressin-neurophysin mRNA (AVP mRNA) was assayed in the pituitary gland of rats from different strains, using a specific cRNA probe corresponding to exon C of the vasopressin gene. Northern blot analysis revealed the presence of an about 650 base pair (bp) AVP mRNA in the neurolobe of all strains. No signal was found in the anterior or intermediate lobes. Partial nucleotide sequence analysis suggested identity with the genuine AVP mRNA. Osmotic stimulation with 2% saline or water deprivation increased AVP mRNA levels in a fashion that paralleled changes seen in the hypothalamus. The origin of the AVP mRNA in the neurolobe is uncertain but is likely to be the pituicytes. Transport of the mRNA into the nerve endings of hypothalamic supraoptic and paraventricular neurons is an alternative possibility.
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PMID:Vasopressin mRNA in the neurolobe of the rat pituitary. 233 83

The solid phase synthesis of three invertebrate vasopressin-oxytocin homologs: AVP-like factor, F1(1), ([Leu2, Thr4] AVT)2 isolated from subesophageal and thoracic ganglia of Locusta migratoria3, Arg-conopressin-S4. ([Ile2, Arg4] AVT), Lys-conopressin-G4 ([Phe2, Arg4] LVT), both isolated from the venom of fish-hunting marine snails of the genus Conus and six of their analogues is reported. These analogues are: [Arg4] AVT, [Ile2] AVT, [Leu2] AVT, [Phe2, Arg4] AVT, [Arg4] LVT and [Ile2, Arg4] LVT. All peptides were tested for antidiuretic and vasopressor activities.
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PMID:Invertebrate neuropeptides resembling vasotocin and some analogues: synthesis and pharmacological properties. 237 7

Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. (3H)-AVP was found to bind to a single class of sites with high affinity (Kd = 2.20 +/- 0.18 nM) and low capacity (Bmax = 17.4 +/- 1.8 fmol/10(6) Leydig cells). Binding displacements with specific selective analogs of AVP indicated the presence of V1 subtype receptors on Leydig cells. The ability of AVP to displace (3H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace (3H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells (P less than 0.001). This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation (P less than 0.01). AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation (P less than 0.001). This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels. We conclude from these data that AVP is capable of modulating steroidogenesis in Leydig cells through specific and functionally V1 receptor subtype and postulate that this effect may be part of an intratesticular paracrine/autocrine control mechanism.
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PMID:Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor. 245 54

The molecular mechanisms which regulate expression of vasopressin (AVP)- and oxytocin (OT)-encoding genes are unknown. We have investigated the regulatory role of one class of second messenger, the cyclic nucleotides, by examining levels of both adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in hypothalamic nuclei of rats during osmotic stimulation. In vivo studies, in which rats were given 2% saline to drink for different periods (salt loading), demonstrated elevated levels of cAMP in the supraoptic nucleus (SON) after 2 days. Raised levels were also evident at 3 and 7 days. A similar (less marked) pattern was observed in the paraventricular nucleus (PVN) but not in the suprachiasmatic nucleus (SCN). cGMP was present at much lower levels than cAMP and did not exhibit parallel dynamics during salt loading; however, significant changes in cGMP levels were found in the SON and PVN. In vitro studies, in which explant cultures of punched hypothalamic nuclei were challenged with hypertonic media, demonstrated that increasing medium osmolality from 290 to 310 mOsm/kg doubled the level of cAMP in the SON but did not change levels in the PVN or SCN. A greater stimulus, 325 mOsm/kg, caused a 4-fold increase in SON cAMP, and small cAMP responses in the PVN and SCN. Marked cGMP responses were also observed in the SON following stimulation at 310 and 325 mOsm/kg, smaller responses being found in the PVN and SCN. These results are consistent with previous demonstrations of SON neuron osmosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic nucleotide dynamics in the rat hypothalamus during osmotic stimulation: in vivo and in vitro studies. 254 82

The in vitro and in vivo oxytocin/arginine vasopressin (OT/AVP) antagonist properties of two cyclic hexapeptides derived from a newly discovered natural product (L-156,373) of Streptomyces silvensis are described. In radioligand binding assays, L-156,373 [cyclo(L-Pro-D-Phe-N-OH-L-Ile-D-piperazyl-L-piperazyl-N-Me-D -Phe)] exhibited moderate affinity for rat uterine OT receptors (Ki, 150 nM), with some selectivity (approximately 20-fold) vs. liver AVP-V1 and kidney AVP-V2 receptors. Dehydroxylation of N-hydroxyisoleucine and oxidation of the piperazic acid residues of L-156-373 produced an interesting derivative, L-365,209. These structural modifications increased OT receptor affinity and selectivity by 20- and 2.5-5-fold, respectively. In the isolated rat uterus, L-365,209 was a potent (apparent dissociation constant, 1.7 nM) and competitive OT antagonist. L-365,209 also blocked the effects of AVP at both AVP-V1 (phosphatidylinositol turnover in rat hepatocytes) and AVP-V2 (adenylate cyclase in rat kidney medulla) receptors, but only at low micromolar concentrations. L-365,209, given iv to anesthetized rats, antagonized the action of exogenous OT on the uterus (ID50, 460 micrograms/kg) with a relatively long duration of action. L-365,209 represents a unique class of compounds that provides an entirely new approach for the design of antagonists for these neurohypophyseal hormones.
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PMID:A structurally unique, potent, and selective oxytocin antagonist derived from Streptomyces silvensis. 254 2

The ontogeny of oxytocin receptors in rat forebrain was studied using the selective oxytocin receptor antagonist 125I-d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH29]OVT [( 125I]-OTA). With in vitro receptor autoradiography, binding wa noted on the first postnatal day in dorsal subiculum and thalamus. On postnatal days 5-18, intense labeling was evident in posterior cingulate cortex, dorsal subiculum, lateral septum, and the CA1 subfield of hippocampus. Of these regions only the lateral septum expressed oxytocin receptors in adult brain. Competition studies on coronal sections through posterior cingulate, septum, and dorsal subiculum at P10 demonstrated that transient binding sites in these areas were indeed oxytocin selective (OXY greater than AVP greater tha V1 greater than V2). Result of saturation studies on cingulate membranes from 10-day-old pups agreed favorably with previous reports of the kinetics of [125I]-OTA binding to adult oxytocin receptors (Kd = 0.1 nM in P10 cingulate cortex vs. 0.07 nM for adult ventral subiculum). In contrast to these evanescent developmental sites, oxytocin receptors in the bed nucleus of the stria terminalis and the ventromedial nucleus of the hypothalamus only appeared in adulthood, presumably in response to the surge of gonadal steroids at puberty.
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PMID:Ontogeny of oxytocin receptors in rat forebrain: a quantitative study. 255 21

The expression of 3 neuropeptide genes, vasopressin (AVP), oxytocin (OT) and somatostatin (SOM), was studied in the developing rat hypothalamus using Northern blot analysis combined with densitometric scanning. A unique profile of developmental expression was established for each of the 3 genes. SOM mRNA is detectable at embryonic day 14 and reaches 40% of the adult levels by embryonic day 18. By contrast, accumulation of AVP and OT mRNA is mainly a postnatal event. AVP mRNA, although detectable in the late embryo, rises gradually after birth and attains 40% of adult levels after the second postnatal week. Maturation of OT gene expression occurs even later and parallels AVP gene expression with a lag time of one week. Observed increases in mRNA levels are due to an upregulation of gene expression since they occur essentially following cessation of neuronal cell proliferation. The rise in AVP and OT mRNA accumulation coincides with the establishment of synaptic input to AVP and OT neurons. Expression of the SOM gene, by contrast, occurs prior to neuronal cell differentiation and points to a possible function of SOM in the embryonic brain.
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PMID:Ontogeny of hypothalamic vasopressin, oxytocin and somatostatin gene expression. 256 76

Continuing our theoretical studies of the oxytocin and vasopressin analogues, we have analysed the molecular electrostatic potential (MEP) and the norm of the molecular electrostatic field (MEF) of [1-beta-mercaptopropionic acid]-arginine-vasopressin ([ Mpa1]-AVP), [1-(beta-mercapto-beta,beta-cyclopentamethylene)propionic acid]-arginine-vasopressin ([Cpp']-AVP), and [1-thiosalicylic acid]-arginine-vasopressin ([Ths']-AVP) whose low-energy conformations were calculated in our previous work. These compounds are known from experiment to exhibit different biological activity. The scalar fields mentioned determine the energy of interaction with either charged (MEP) or polar (MEF) species, the energy being in the second case either optimal or Boltzmann-averaged over all the possible orientations of the dipole moment versus the electrostatic field. The electrostatic interactions slowly vanish with distance and can therefore be considered to be the factor determining the molecular shape at greater distances, which can help in both predicting the interactions with the receptor at the stage of remote recognition and in finding the preferred directions of solvation by a polar solvent. In the analysis of the fields three techniques have been used: (i) the construction of maps in certain planes; (ii) the construction of maps on spheres centered in the charge center of the molecule under study and of poles chosen according to the main axes of the quadrupole moment; and (iii) the construction of surfaces corresponding to a given value of potential. The results obtained show that the shapes of both MEP and MEF are similar in the case of [Mpa1]-AVP and [Cpp1]-AVP (biologically active), while some differences emerge when comparing these compounds with [Ths1]-AVP (inactive). It has also been found that both MEP and MEF depend even more strongly on conformation.
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PMID:Theoretical studies of the mechanism of the action of the neurohypophyseal hormones. I. Molecular electrostatic potential (MEP) and molecular electrostatic field (MEF) maps of some vasopressin analogues. 258 2

Endogenous opioids inhibit the release of oxytocin (OT) when vasopressin (AVP) is secreted in response to acute pharmacological stimuli in man and to a variety of physiological and pharmacological stimuli to animals. We have investigated the effect of naloxone on the AVP and OT responses to hypertonic saline in man. In two separate studies, six male subjects were infused with hypertonic saline (675 mmol/l, 0.05 ml/kg/min for 2 h) and either naloxone (4 mg bolus and 6 mg/h) or normal saline in random order. Hypertonic saline resulted in similar significant rises of plasma osmolality and AVP in both groups and a small but significant decrease in OT. Thirst sensation was not altered by naloxone. Endogenous opioids do not play an important role in the suppression of OT release when AVP is secreted in response to an osmotic stimulus in man.
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PMID:Vasopressin and oxytocin responses to hypertonic saline infusion: effect of the opioid antagonist naloxone. 260 88

The self-assembly properties of the arginine 8-vasopressin/bovine neurophysin II (AVP/BNPII) biosynthetic precursor were studied using glycopeptide-deleted and sequence-redesigned semisynthetic derivatives. Semisynthetic precursors were prepared by chemically coupling synthetic vasopressinyl sequence domains and native protein-derived neurophysin II domain. Measurement of precursor-protein association by the extent of affinity chromatographic retardation on agarose-immobilized BNPII verified that the semisynthetic precursor with native AVP sequence has an enhanced self-association propensity similar to that predicted for native precursor. Here, the stabilizing contacts between hormone and neurophysin domains, mainly the positively charged protonated alpha-amino group and tyrosyl 2 side chain of the hormone, are retained. Semisynthetic precursor variants in which the hormone domain is sequence-simplified by introducing alanyl residues in positions not considered important for neurophysin recognition show non-reduced association to BNPII. In contrast, removal of one of the main contact elements between hormone and neurophysin by acetylation of the hormone alpha-amino group abolishes potentiation of precursor self-association. The results show that the presence of the C-terminal glycopeptide sequence domain of native vasopressin precursor is not required to promote self-assembly of the precursor. The data verify the view proposed for the oxytocinyl precursor that intramolecular domain interaction is the triggering event which promotes the increase in affinity of precursor self-association (intermolecular self-recognition). The data also define some of the intramolecular self-recognition elements in the folded precursor required for the high affinity intermolecular self-recognition.
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PMID:Sequence simplification and the intra- and intermolecular self-recognition properties of vasopressin/neurophysin biosynthetic precursor. 263 63


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