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)

As part of a continuing investigation of the steric and electronic functions of the disulfide group in neurohypophyseal hormones on their biological activity, the synthesis of "oxytocin lactam", [cyclo-(1-aspartic acid,6-alpha,beta-diaminopropionic acid)]oxytocin, has been undertaken. The protected nonapeptide was prepared in a stepwise manner by solution techniques; after removal of side-chain protecting groups, formation of the briding amide bonds was accomplished by oxidation-reduction condensation. The analogue possesses rat uterotonic, avian vasodepressor, and rat antidiuretic potencies of 16 +/- 2, 6.6 +/- 0.6, and 5.6 +/- 3.8 units/mg, respectively.
 ...
PMID:Replacement of the disulfide bond in oxytocin by an amide group. Synthesis and some biological properties of (cyclo-(1-L-aspartic acid,6-L-alpha,beta-diaminopropionic acid))oxytocin. 61 41

1. Recently it has been shown that injection of angiotensin II into the anterior diencephalon causes the rat to drink water. In the present experiments the dipsogenic action of a number of other substances including substances related to angiotensin was tested.2. Injection of 0.001 Goldblatt u. renin into the angiotensin-sensitive region causes the water-replete rat to drink. Drinking is slower in onset and continues for longer than after injection of angiotensin II.3. Synthetic tetradecapeptide renin substrate and angiotensin I were as effective as angiotensin II at causing water-replete rats to drink.4. beta-aspartic acid(1)-valine(5)-angiotensin II was also fully effective; but the D-arginine substituted octapeptide was much less effective.5. The (2-8) heptapeptide retained about 50% of the dipsogenic activity of the octapeptide, whereas the absence of phenylalanine at the other end of the peptide chain in the (1-7) heptapeptide results in an inactive compound.6. The (3-8) hexapeptide and the (4-8) pentapeptide, both of which have phenylalanine at the end of the chain, and the (1-4) and (5-8) tetrapeptide fragments of angiotensin II showed only a slight action on intake of water.7. Kallikrein, bradykinin, adenosine-3'5-cyclic phosphate, vasopressin and oxytocin caused no drinking when injected into the angiotensin-sensitive region.8. It is concluded that the requirements for the dipsogenic activity of angiotensin are the same as those for its other biological actions with the qualification that the precursor peptides are also active, presumably because they give rise to angiotensin II locally.
 ...
PMID:The effect on drinking of peptide precursors and of shorter chain peptide fragments of angiotensin II injected into the rat's diencephalon. 432 62

Application of information derived from a three-dimensional model of vasopressin bound to its antidiuretic receptor resulted in the design and synthesis of a bicyclic vasopressin analog, [5,8-cyclo(1-beta-mercaptopropionic acid,2-phenylalanine,5-aspartic acid,8-lysine)]vasopressin. The analog acts as an antagonist of the antidiuretic activity of vasopressin.
 ...
PMID:A conformationally constrained vasopressin analog with antidiuretic antagonistic activity. 654 6

Studies were carried out on the right auricle of the right atrium of two-day-old rats placed in a special chamber perfused with Ringer-Locke solution at room temperature. The contractions rate of the auricle was counted with the use of a stereomicroscope. The following amino acids dissolved in Ringer-Locke solution were tested: glycine, glutamic acid, serine, alanine, aspartic acid, gamma aminobutyric acid, leucine, and peptides: vasopressin and oxytocin. Glutamic acid in a concentration of 10(-1) mol/l induced a decrease in auricle contraction rate by 25%. Alanine in concentration 10(-2) mol/l induced a decrease by 22%. Leucine in concentration 10(-2) mol/l induced a decrease by 16% and in concentration ten times higher a decrease by 28%. The other tested amino acids, vasopressin and oxytocin in concentration used had no influence on the rate of contraction frequency of the isolated auricle.
 ...
PMID:The influence of amino acids, vasopressin and oxytocin on spontaneous contraction of the right auricle of the right atrium of two-day-old rats in vitro. 654 86

In chronically cannulated conscious chickens, Gallus gallus, native chicken angiotensin II ([Asp1,Val5]ANG II) caused biphasic blood pressure responses, a depressor followed by a pressor response. The pressor response appears to be mediated primarily by catecholamines. The depressor responses increased with increasing doses and were accompanied by tachycardia. The onset of the depressor action of [Asp1,Val5]ANG II (2.49 +/- 0.22 s) was nearly as quick as that of acetylcholine or histamine. Replacement of aspartic acid in position 1 with sarcosine or asparagine reduced both depressor and pressor potencies, whereas there was no difference either in depressor or pressor potencies between [Asp1,Val5] and [Asp1,Ile5]ANG II. The depressor response to [Asp1,Val5]ANG II was not inhibited by atropine, a vasopressin antagonist, prostaglandin synthetase inhibitors, methysergide, or propranolol but was blocked markedly by [Sar1, Ile8]ANG II and partially by [Sar1,Thr8]ANG II. The results suggest that the vasodepressor action of ANG II is mediated by angiotensin receptors and may possibly be a direct action on the vascular smooth muscle.
 ...
PMID:Vasodepressor action of angiotensin in conscious chickens. 711 76

In the proposed biologically active conformation of vasopressin at its antidiuretic receptor, the side-chain carboxamide moiety of the 5-position asparaginyl residue has been suggested to be an active element for the initiation of the antidiuretic response. [5-Aspartic acid] arginine vasopressin, the analog in which the -NH2 portion of the primary amide has been replaced by an -OH group, has been synthesized and tested for some of the pharmacological activities of vasopressin. The partially protected nonapeptide intermediate was assembled bidirectionally on a poly-N-acrylylpyrrolidine resin. The 6-position cysteinyl residue was attached to the resin via its side-chain through an S-carbamoyl linkage. First the COOH-terminus was extended by coupling with Pro-Arg(Tos)-Gly-NH2, then the NH2-terminus was extended in a stepwise manner. [5-Aspartic acid] arginine vasopressin was found to possess 86.5 +/- 4.8 units/mg of antidiuretic potency, 17% of the parent hormone. In addition, the analog possesses rat pressor and rat uterotonic potencies of 6.93 +/- 0.15 and 0.38 +/- 0.03 units/mg, respectively. This result suggests that a carboxylic acid moiety on the 5-position aspartyl residue retains sufficient steric features and hydrophilicity in common with the carboxamide moiety present in the hormone to substitute for it as an active element at the antidiuretic receptor.
 ...
PMID:Bidirectional synthesis of [5-aspartic acid] arginine vasopressin on poly-N-acrylylpyrrolidine resin. 721 12

Oxytocin (OT) release within the brain is thought to play a major role in inducing maternal behaviour in a number of mammalian species but little is known about the sites of release which are important in this respect. We have investigated whether the paraventricular nucleus of the hypothalamus (PVN) is a site of OT action on maternal behaviour in the sheep. In vivo microdialysis and retrodialysis was used to determine whether OT is released in the region of the PVN during the post-partum induction of maternal behaviour and if its release at this site can stimulate maternal behaviour in non-pregnant animals. In vivo sampling showed that OT concentrations increased significantly in the region of PVN at birth. When OT was retrodialysed bilaterally into the PVN (1 or 10 microM) of multiparous ewes treated with progesterone and oestradiol to stimulate lactation, maternal behaviour was induced in a significant number of animals (1 microM, 6/8 and 10 microM, 5/8) compared with controls (0/8 ewes). Similar infusions of the ring structure of OT, tocinoic acid (TOC-10 microM), also induced maternal behaviour in a significant proportion of animals (5/6 ewes) as did intracerebroventricular (ICV) OT (6/8 ewes) and artificial stimulation of the vagina and cervix (VCS, 8/9 ewes). On the other hand, vasopressin (AVP) 1 microM did not induce maternal behaviour in any ewes and a 10 microM dose only induced it in 2/8 animals. The neurochemical changes accompanying the above treatments were also investigated. Noradrenaline concentrations increased in the PVN after the retrodialysis administration of OT 1 microM and 10 microM, TOC 10 microM and AVP 1 microM, OT ICV and VCS. Dopamine concentrations were also increased by OT 10 microM, TOC 10 microM, AVP 1microM and OT ICV. Aspartate and glutamate concentrations were significantly reduced by retrodialysis infusions of OT 1 microM and AVP 1 and 10 microM but not by any other treatment. Finally, the retrodialysis infusion of OT and TOC, as well as ICV OT, significantly increased plasma OT release whereas AVP infusions did not. These results provide evidence that OT is released in the PVN during parturition and is important for the induction of maternal behaviour. It seems probable that OT release at this site has a positive feedback effect on both parvocellular and magnocellular OT neurons to facilitate co-ordinated OT release both in central OT terminal regions (to facilitate maternal behaviour) and peripherally into the blood (to facilitate uterine contractions/milk let down). The potential functional roles for the actions of OT on monoamine and amino acid transmitter release in the PVN are discussed.
 ...
PMID:The role of oxytocin release in the paraventricular nucleus in the control of maternal behaviour in the sheep. 873 Jun 50

In order to evaluate the role played by vasopressin on pressor responses elicited by stimulation of the periaqueductal gray (PAG) area by excitatory amino acids we carried out in vivo studies in genetically vasopressin deficient rats (Brattleboro). Microinjections of 1-glutamic acid (glutamate, 0.6 to 60 nmol/rat) or N-methyl-d-aspartic acid (NMDA, 0.07 to 7 nmol/rat) into the PAG area of freely moving Brattleboro rats induced increases of arterial blood pressure values significantly lower than those obtained in Long Evans rats (control) (glutamate in Brattleboro rats: from +2+/-1 mmHg to 16+/-3 mmHg; glutamate in Long Evans rats: from +16+/-2 mmHg to +36+/-4 mmHg; NMDA in Brattleboro rats: from +5+/-2 mmHg to +34 +/-8 mmHg; NMDA in Long Evans rats: from +18+/-7 mmHg to 80+/-9 mmHg; n=5). Similarly, in anaesthetized Brattleboro rats (urethane 1.2 g/kg i.p.) pressor responses to NMDA microinjections (0.7 nmol/rat) into the PAG area were significantly lower than in Long Evans rats (controls) (+15+/-3 mmHg vs +24+/-4 mmHg). In Long Evans rats NMDA injection also reversed blood pressure decrease induced by ganglionic blocker, hexamethonium and/or losartan (3 mg/kg i.v.), an AT1 receptor antagonist. In Brattleboro rats, NMDA injection did not reverse blood pressure decreases induced by hexamethonium (5 mg/kg i.v.). Moreover, hexamethonium induced blood pressure decrease was not reversed by acetylcholine injection (137 nmol/rat) into the PAG area of anaesthetized Long Evans rats, but if injected before hexamethonium, acetylcholine was able to increase blood pressure (+25+/-3 mmHg). Our results document: i) the importance of the PAG area in the control of cardiovascular system; ii) the involvement of excitatory amino acids in the neural control of vasopressin release; iii) the close relationship between glutamate and vasopressin in the central blood pressure regulation.
 ...
PMID:Role of vasopressin on excitatory amino acids mediated pressor responses in the periaqueductal gray area. 965 Aug 3

In chickens, oviposition is correlated with increased plasma levels of the neurohypophysial hormone vasotocin, and vasotocin stimulates contraction of uterine strips in vitro. A gene encoding a vasotocin receptor subtype that we have designated the VT1 receptor was cloned from the domestic chicken. The open reading frame encodes a 370-amino acid polypeptide that displays seven segments of hydrophobic amino acids, typical of guanine nucleotide-protein-coupled receptors. Other structural features of the VT1 receptor include two potential N-linked glycosylation sites in the extracellular N-terminal region, a conserved aspartic acid in transmembrane domain 2 that is found in nearly all guanine nucleotide-protein-coupled receptors, and two potential protein kinase C phosphorylation sites in the third intracellular loop and C-terminal tail. Expressed VT1 receptors in COS7 cells bind neurohypophysial hormones with the following rank order of potency: vasotocin congruent with vasopressin > oxytocin congruent with mesotocin > isotocin. In addition, the expressed VT1 receptor mediates vasotocin-induced phosphatidylinositol turnover and Ca(2+) mobilization. In the chicken, expression of VT1 receptor gene transcripts is limited to the shell gland (uterus) and the brain. Thus, the VT1 receptor that we have cloned may mediate contractions of the shell gland during oviposition and activate reproductive behaviors known to be stimulated by vasotocin in lower vertebrates.
 ...
PMID:Molecular cloning and functional characterization of a vasotocin receptor subtype that is expressed in the shell gland and brain of the domestic chicken. 1061 Oct 61

The aim of this study was to identify loss-of-function mutations of the V2 vasopressin receptor gene (AVPR2) in Italian patients affected by X-linked nephrogenic diabetes insipidus (NDI). Mutations were found in 15 of the 18 unrelated families investigated: nine of these mutations were previously unknown, including two affecting residues located in regions known to be important for determining the pharmacologic properties of the receptor, which were therefore functionally investigated. The first (A84D) involves a residue located near an aspartic acid (D85) that is highly conserved in all G protein-coupled receptors and that is believed to play a role in the process of their isomerization into functionally active and inactive states. The present study indicates that this mutation not only affects receptor folding in such a way as to lead to its retention inside the intracellular compartments but, as expected, also has profound effects on its binding and coupling properties. The second was a mutation of a tryptophan located at the beginning of the first extracellular loop (W99R) that greatly impaired the binding properties of the receptor and had a minor effect on its intracellular routing. Molecular analysis of the first extracellular loop bearing this mutation suggests that this residue plays a fundamental role in stabilizing the peptide/receptor interactions responsible for the high-affinity binding of agonists to the V2 receptor.
 ...
PMID:Nephrogenic diabetes insipidus: functional analysis of new AVPR2 mutations identified in Italian families. 1082 Jan 67


1 2 Next >>