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

Using the Merrifield solid-phase method, we have synthesized 18 new 2-O-alkyltyrosine-substituted analogues (where alkyl = methyl and ethyl) of the arginine-vasopressin (AVP) vasopressor antagonists [1-deaminopenicillamine]-arginine-vasopressin (dPAVP), [1-(beta-mercapto-beta,beta-diethylpropionic acid)]arginine-vasopressin (dEt2AVP), and [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)]arginine-vasopressin (d(CH2)5AVP) and of their 8-D-arginine (d(R2)DAVP) analogues, their 4-valine (dR2VAVP) analogues, and their 4-valine,8-D-arginine (d(R2)VDAVP) analogues [where R = CH3 or C2H5 and 2R = (CH2)5]. These analogues were tested for agonistic and antagonistic activities in in vivo rat vasopressor and rat antidiuretic and in vitro rat uterus assay systems. Although many exhibit very low antidiuretic activities, none of the new analogues antagonize antidiuretic responses to AVP. They exhibit no evident pressor activities and are in fact all highly effective antagonists of the vasopressor responses to AVP. They are also potent antagonists of the in vitro oxytocic responses to oxytocin, both in the absence and in the presence of Mg2+. These analogues together with their corresponding antivasopressor pA2 values are as follows: 1. dPTyr(Et)AVP, 8.40 +/- 0.08; 2. dEt2Tyr(Me)AVP, 8.53 +/- 0.06; 3. dEt2Tyr(Et)AVP, 8.46 +/- 0.08; 4. d(CH2)5Tyr(Et)AVP, 8.47 +/- 0.04; 5. dPTyr(Me)DAVP, 8.31 +/- 0.08; 6. dPTyr(Et)DAVP, 8.27 +/- 0.06; 7. dEt2Tyr(Me)DAVP, 8.57 +/- 0.03; 8. dEt2Tyr(Et)DAVP, 8.33 +/- 0.06; 9. d(CH2)5Tyr(Me)DAVP, 8.41 +/- 0.05; 10. d(CH2)5Tyr(Et)DAVP, 8.45 +/- 0.05; 11. dPTyr(Me)VAVP, 8.36 +/- 0.07; 12. dPTyr(Et)VAVP, 8.07 +/- 0.13; 13. dEt2Tyr(Me)VAVP, 8.29 +/- 0.08; 14. dEt2Tyr(Et)VAVP, 8.42 +/- 0.06; 15. dPTyr(Me)VDAVP, 7.84 +/- 0.06; 16. dPTyr(Et)VDAVP, 8.46 +/- 0.03; 17. dET2Tyr(Me)VDAVP, 8.35 +/- 0.10; 18. dEt2Tyr (Et)VDAVP, 8.19 +/- 0.07. Seven of these analogues are clearly more potent vasopressor antagonists than their respective unalkylated tyrosine-containing parents. In the remaining 11, antagonistic potency was not changed significantly. In no instance did 2-O-alkyltyrosine substitution decrease antagonistic potency. With pA2 values equal to or greater than 8.40, nine of these antagonists (numbers 1-4, 7, 9, 10, 14, and 16) are among the most potent vasopressor antagonists reported to date. They could thus serve as additional valuable pharmacological tools in studies on the roles of AVP in the control of blood pressure in normal and in pathophysiological conditions. These findings may also provide useful clues to the design of more potent and selective antagonists of AVP.
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PMID:Synthesis and some pharmacological properties of 18 potent O-alkyltyrosine-substituted antagonists of the vasopressor responses to arginine-vasopressin. 404 23

Arginine-vasopressin caused platelet activation, i.e., a shape change reaction and a rise in intracellular free Ca2+ ([Ca2+]i) only in the presence of certain bivalent cations. The EC50 of arginine-vasopressin (concentration causing half-maximal shape change) decreased with rising concentrations of Mn2+, Mg2+, or Ca2+ in the medium, but was at least an order higher with Ca2+ than with Mn2+ or Mg2+. The EC50 of the active bivalent cations (concentrations enabling 100 nM arginine-vasopressin to exert half-maximal shape change and rise in [Ca2+]i) varied with the individual cations, being by far the highest for Ca2+. The KD of [3H]arginine-vasopressin binding to platelet membranes and intact platelets markedly decreased when extracellular Mg2+ or Mn2+ were present, and the KD values were inversely related to the concentration of the cations. Ca2+ also lowered the KD values; however, the effect was less marked than that of Mg2+ or Mn2+ and, in physiological conditions, significant only in intact platelets. Vasopressin-1 antagonists counteracted arginine-vasopressin binding and the shape change reaction and [Ca2+]i rise induced by arginine-vasopressin. In the presence of Mn2+ in the medium, administration of arginine-vasopressin led to quenching of the intracellular fluorescence of 2-methyl-6-methoxy-8-nitroquinoline-loaded platelets, possibly due to influx of Mn2+. In conclusion, the dependency of the arginine-vasopressin-induced platelet activation on bivalent cations is at least partly due to an enhancement by these cations of the affinity of the vasopressin-1 receptor for arginine-vasopressin. Thereby, under physiological conditions, Mg2+ seems to be of primary importance. Other mechanisms may be involved, too, e.g., an enhancement by arginine-vasopressin of the influx of bivalent cations into the platelets.
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PMID:Activation of human blood platelets by arginine-vasopressin. Role of bivalent cations. 407 9

Synthetic [8-arginine]-vasopressin, [8-lysine]-vasopressin, [8-ornithine]-vasopressin or [2-phenylalanine, 8-lysine]-vasopressin aggregated human platelets in heparinized platelet-rich plasma. The lowest effective concentrations (1-4mU/ml) caused a primary transient aggregation, while higher concentrations also caused a secondary irreversible aggregation. Vasopressin was almost inactive in citrated platelet-rich plasma but caused aggregation in recalcified citrated or native material. Vasopressin also aggregated washed human platelets suspended in buffered saline, if fibrinogen and either Ca2+ or Mg2+ ions were present. Ethylene glycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid inhibited aggregation completely but only after preincubation with the platelets, suggesting that platelet-bound calcium was also required. Phosphocreatine with creatine phosphokinase partially inhibited primary aggregation of platelets by vasopressin and prevented secondary aggregation, which suggests that release of platelet ADP contributed to these processes. Concentrations of vasopressin causing irreversible aggregation released small amounts of 14C from platelets containing serotonin-14C. Platelet aggregation induced by vasopressin was inhibited by adenosine, prostaglandin E1, N6,2'-0-dibutyryl cyclic 3',5'-AMP, caffeine, imipramine, or N-ethylmaleimide. Adenosine and prostaglandin E each inhibited the action of vasopressin much more powerfully than that of ADP and, therefore, cannot act solely by inhibiting the effects of the ADP released. In several respects the effect of vasopressin on blood platelets resembled its action on smooth muscle.
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PMID:Aggregation of human blood platelets by vasopressin. 434 80

In this study we have characterized binding sites for ovine corticotropin-releasing factor (oCRF) in the rat anterior pituitary gland, and have investigated whether the site of interaction of vasopressin and oCRF is at the plasma membrane level. The binding 125I-oCRF to anterior pituitary membranes was shown to be dependent on temperature, pH and cation concentration. Magnesium was essential for the binding reaction to take place. Two binding sites of Kd 7.63 X 10(-10) and 3.39 X 10(-8) M were found. Activity of adenylate cyclase in the membrane preparation increased in the presence of oCRF. The activity of the enzyme as well as the binding of 125I-oCRF was found to be influenced by guanosine-5'-triphosphate. Several hypothalamic neurohormones, including vasopressin, failed to alter the binding of 125I-oCRF to anterior pituitary membranes. Moreover, vasopressin failed to influence the stimulation of adenylate cyclase activity induced by oCRF. Preincubation of anterior pituitary segments with oCRF desensitized the corticotropin (ACTH) response to oCRF and decreased the amount of 125I-oCRF bound to membranes prepared from similarly treated pituitaries. The ACTH response to vasopressin remained unchanged. Following a preincubation of anterior pituitary segments with vasopressin, oCRF stimulated ACTH secretion, as well as the binding of 125I-oCRF to pituitary membranes was normal, while the ACTH response to vasopressin was markedly reduced. These results show that separate receptors mediate the action of vasopressin and oCRF. Moreover, the ACTH response to vasopressin and oCRF may be modulated separately.
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PMID:Pituitary receptors for corticotropin-releasing factor: no effect of vasopressin on binding or activation of adenylate cyclase. 608 19

The effects of arginine-vasopressin (AVP) on the excitability of 47 pyramidal cells of the CA1 region of the hippocampus were determined by using intracellular recording techniques in a submerged slice preparation. Addition of 10(-6) M AVP to the bathing medium evoked an increase in spike discharge which was slow in onset and only gradually reversible. The discharge was accompanied by an increase in excitatory postsynaptic potentials without significant change of the resting input resistance. AVP-induced excitation was found in 81% of ventral and 29% of dorsal hippocampal CA1 pyramidal cells. In low Ca2+, high Mg2+ solution this excitatory action by AVP was blocked. Microiontophoretic application of AVP onto apical or basal dendrites or the cell body did not result in excitation. These observations suggest that the action of AVP on CA1 pyramidal cells is transsynaptic and is more pronounced in ventral than dorsal CA1.
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PMID:Action of vasopressin on CA1 pyramidal neurons in rat hippocampal slices. 608 58

A high affinity Ca2+-stimulated, Mg2+-dependent ATPase (Ca2+-Mg2+-ATPase) was identified in microsomes and plasma membrane vesicles isolated from rat hepatocytes. The distribution of this enzyme was similar to that of the plasma membrane marker enzymes alkaline phosphodiesterase and 5'-nucleotidase. The Ca2+-Mg2+-ATPase had an apparent half-saturation constant of approximately 75 nM for Ca2+. After incubation of rat hepatocytes with 25 nM vasopressin for 3 min, the activity of Ca2+-Mg2+-ATPase was decreased 15-30%. The effect of vasopressin on the activity of this enzyme was near maximal after incubating hepatocytes with vasopressin for only 15 sec. The concentration of vasopressin needed for half-maximal inhibition of this enzyme in hepatocytes was approximately 6 nM. Treatment of the hepatocytes with 10 microM phenylephrine caused about a 10% decrease in ATPase activity while 10 nM glucagon or 200 microU/ml insulin did not affect the enzyme. These findings suggest that inhibition of the Ca2+-Mg2+-ATPase activity may be part of the mechanism by which vasopressin and alpha-adrenergic agonists elevate cytosolic Ca2+ in hepatocytes.
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PMID:Regulation of Ca2+-Mg2+-ATPase activity in hepatocyte plasma membranes by vasopressin and phenylephrine. 613 76

A crude membrane fraction prepared from bovine adrenal medulla bound tritium labeled arginine-vasopressin (3H-AVP) in a time and temperature dependent manner. Physiological concentrations of Mg2+ (1-3 mmol/l) were required for the binding reaction, while Ca2+ (5-80 mmol/l) had no effect. The reaction was saturable and reversible. Scatchard plots of the data suggested the presence of a single class of high affinity (Kd=0.41 nmol/l) and low capacity (Bmax=26 fmol/mg protein) binding sites. The specificity of the binding reaction was examined using various structural analogs of AVP which displaced 3H-AVP. Arginine-vasotocin proved to be equipotent with AVP, while oxytocin and 1-deamino,8-D-arginine-vasopressin were about 500-fold less effective. Two relatively selective V1-receptor antagonists, dPenTyrMeAVP and d(CH2)5-TyrMeAVP were 2- and 20-fold less potent than AVP, respectively These data strongly suggest that the bovine adrenal medulla contains V1-type receptors for vasopressin, which could be involved in the regulation of the function of chromaffin cells.
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PMID:Characterization of high affinity binding sites for vasopressin in bovine adrenal medulla. 623 39

The present study investigated whether specific [3H]oxytocin binding sites previously demonstrated in estrogen-dominated rabbit uterus have properties expected of physiologic receptors coupled to uterine contraction. Microsomal membranes from estrogen-dominated rabbit uterus were found to contain high-affinity specific oxytocin binding sites with Kd = 2-3 nM. These sites were predominantly myometrial in locus. Specific oxytocin binding exhibited a pH optimum between 7.5 and 8.0. Mg2+ or Mn2+ was necessary for maximal specific [3H]oxytocin binding; in contrast, Ca2+ at submillimolar concentrations inhibited specific binding. Oxytocin binding sites were not detectable in microsomal membranes isolated from progesterone-dominated rabbit uterus. Relative binding and uterotonic activities of 10 synthetic neurohypophyseal hormone analogues were determined in estrogen-dominated rabbit uterus. A qualitative correlation was observed between binding and uterotonic responses. Angiotensin II and insulin did not compete with [3H]oxytocin for uterine binding sites. It is concluded that the specific high affinity [3H]oxytocin binding sites demonstrated in estrogen-dominated rabbit uterus have the selectivity for neurohypophyseal hormone analogues expected for physiologic receptors coupled to uterine contraction.
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PMID:Oxytocin receptors coupled to uterine contraction in estrogen-dominated rabbits. 624 2

Liver plasma membrane adenylate cyclase was stimulated paradoxically by an alpha 2-adrenergic mechanism under conditions of low metal ion and low GTP concentrations. In untreated membranes, epinephrine stimulation was GTP-dependent and was mediated by beta-adrenergic receptors since it was completely blocked by propranolol, but unaffected by dihydroergocryptine. Pre-treatment of membranes to remove or reduce divalent cations and guanine nucleotides changed epinephrine stimulation to a form that was mediated by alpha 2-receptors since it was completely blocked by dihydroergocryptine, phenoxybenzamine and yohimbine, but not by propranolol or prazosin. The pre-treatment did not alter enzyme activation by isoproterenol or glucagon, alpha 2-Adrenergic stimulation of adenylate cyclase in depleted membranes required the presence in the assay of 1-2 mM Mg2+ and small amounts of exogenous GTP (less than or equal to 50 nM). Increasing the Mg2+ or GTP concentration in the assay produced a progressive reversal of epinephrine-stimulated activity from an alpha 2-adrenergic form to a predominantly beta-adrenergic form. Readdition of Ca2+ or Mg2+, but not Mn2+, into depleted membranes by incubation in the presence of metal reestablished the pattern of enzyme sensitivity to epinephrine to that seen with untreated membranes i.e., it changed from alpha 2- to beta-receptor mediation. Alterations in membrane and assay content of metal ions and GTP did not result in the activation of the enzyme by vasopressin or angiotensin II. These findings demonstrate the ability of Ca2+, Mg2+ and GTP to control the coupling of beta- and alpha 2-adrenergic receptors with liver adenylate cyclase. It is hypothesized that the cations act by regulating the interaction of the receptors with adrenergic agonists and/or the guanine nucleotide binding protein(s) which is postulated to be involved in control of the enzyme.
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PMID:Regulation of adrenergic stimulation of hepatic adenylate cyclase by divalent cations. 627 6

Brain slices of the guinea-pig hypothalamus were used to determine the effects of vasopressin on intracellular potentials in neurones of the supraoptic nucleus. Vasopressin (0.05-1 i.u./ml.) depolarized the membrane without apparent change in the input resistance and decreased the spontaneous firing rate. This action of vasopressin was retained in the medium containing 0 mM-Ca2+, 12 mM-Mg2+ and 0.3 mM-EGTA. Amplitude of the vasopressin-induced depolarization was voltage-independent. Ion-substitution experiments showed that the changes in [K+]o, [Cl-]o and [Ca2+]o had little effect upon the amplitude of vasopressin-induced depolarization, whereas the depletion of [Na+]o slightly reduced the amplitude. The vasopressin-induced depolarization was blocked at a temperature of 15 degrees C and by ouabain in a dose of 10(-4) M. Dibutyryl cyclic AMP (2 mM) produced electrophysiological effects similar to those seen with vasopressin, and actions of both agents were potentiated by either papaverine (10(-4) M) or theophylline (10(-2) M). Contents of cyclic AMP in tissues incubated with vasopressin were significantly higher than in cases of incubation with normal Krebs solution. We conclude that vasopressin directly modulates the activity of supraoptic neurones, possibly through activation of adenylate cyclase.
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PMID:The effects of vasopressin on electrical activity in the guinea-pig supraoptic nucleus in vitro. 630 38


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