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)

Reaction of tetranitromethane with the lone tyrosine residue of bovine neurophysin I and II, tyrosine-49, gave nitro derivatives of these proteins which were obtained in a highly purified form by preparative electrophoresis. Equilibrium dialysis experiments indicated clearly that oxytocin binding remained essentially unaffected by the chemical modification of tyrosine-49. However, in the case of (8-lysine)vasopressin, the nitrated protein was found to bind only 1 hormone molecule in contrast to the 2 vasopressin molecules bound by the native protein. Ultraviolet absorption difference spectroscopy measurements between 250 nm and 300 nm indicated that upon binding of (2-phenylalanine, 8-lysine)vasopressin, tyrosine-49 of native neurophysin undergoes a change of microenvironment from less to more polar surroundings. Studies of the nitrotyrosyl-49 chromophore of neurophysin by ab sorption spectroscopy in the absence and presence of oxytocin or (8-lysine)vasopressin confirmed this finding. Since dimethylsulfoxide solvent perturbation studies suggested that in the Cys(Me)-Phe-Ile-NH2-neurophysin I complex, tyrosine-49 is more exposed to solvent than in neurophysin I alone, it is concluded that this residue is unmasked by conformational changes upon complex formation.
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PMID:Interactions of bovine neurophysins with neurohypophyseal hormones. On the role of tyrosine-49. 115 Jun 56

The effect of vasopressin analogues on plasma adenosine 3',5'-cyclic monophosphate (cAMP) concentration was examined in a group of five conscious dogs instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter). These dogs were infused for 20 min with a selective antidiuretic (V2) agonist, desamino-8-D-arginine vasopressin (DDAVP, 10 ng.kg-1 x min-1). This infusion was repeated on another day in the presence of the combined V1-V2 antagonist d(CH2)5-D-Tyr(Et)-4-valine,8-arginine vasopressin. The dogs also received an infusion of the selective V1 agonist 2-phenylalanine,8-ornithine oxytocin (Phe-OrnOT) at a rate of 10 ng.kg-1 x min-1. The effect of these infusions was compared with those of an isotonic saline infusion. Plasma cAMP measured in the aorta remained unchanged during all infusions but that of the selective V2 agonist DDAVP alone, during which it increased significantly from 22.4 +/- 0.8 to 32.6 +/- 4.6 and 37.0 +/- 4.1 pmol/ml after 10 and 20 min, respectively. In the plasma sampled from the inferior vena cava caudal to the renal veins, cAMP increased during DDAVP infusion from 22.2 +/- 2.5 to 39.2 +/- 3.8 and 36.0 +/- 4.0 pmol/ml after 10 and 20 min, respectively. The infusion of DDAVP was later given to the same dogs under anesthesia after bilateral nephrectomy, which did not modify the effect of DDAVP on arterial plasma cAMP. In another group of four conscious dogs, infusion of DDAVP at the same rate did not induce significant changes in plasma catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:cAMP and extrarenal vasopressin V2 receptors in dogs. 133 16

The isolated rat hindquarter preparation perfused at constant flow was used to determine resistance and capacitance responses from pressure and weight recordings. In response to noradrenaline at low concentrations, the capacitance effect was greater than the relative increase in total vascular resistance. 8-L-Arginine vasopressin showed capacitance responses only when the resistance vessel constriction was pronounced. Oxytocin and two synthetic analogues, 2-phenylalanine-8-ornithine vasopressin (Phe-Orn-VP) and 2-phenylalanine-8-ornithine oxytocin, showed varying potency for resistance vessel constriction but hardly any capacitance responses. However, when Phe-Orn-VP induced a small increase in total vascular resistance, a marked increase in post-capillary resistance was observed. The results are discussed in relation to a study in which the effects of vasopressin analogues were studied with intravital microscopy (Altura 1973).
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PMID:Effects of noradrenaline and vasopressin analogues on resistance and capacitance vessels in the rat hindquarter preparation. 235 60

The effect of arginine vasopressin (AVP) on the duration and the relative proportion of sleeping and wakeful periods has been investigated. Vigilance states were determined by visual scoring of polygraphic recordings from unrestrained rats. Animals were implanted with a cannula into the third ventricle through which AVP or related drugs, dissolved in artificial cerebrospinal fluid, were infused at a constant rate by an osmotic pump. Polygraphic data were collected 24 h/day from day 4 to day 9. Recordings were continued for 3 additional days during AVP recovery. AVP infusions significantly increased the amount of time spent in waking compared with control or recovery periods (12%). This effect was mimicked by an AVP agonist (2-phenylalanine, 8-ornithine oxytocin). Oxytocin, a peptide structurally close to AVP, induced a mild change in waking time. The infusion of an AVP antagonist, 1-desaminopenicillamine-2-(O-methyl)tyrosine-arginine vasopressin (dPTyr(Me)AVP), or of anti-AVP antibodies significantly decreased duration of waking. The infusion of antioxytocin antibodies did not modify the duration of waking. The effects of structural analogues of AVP relatively specific for each type of peripheral AVP receptor indicated the participation of a V1-like AVP receptor in the action of AVP on waking time. During infusion of anti-AVP antibodies and dPTyr(Me)AVP and during the first days of recovery from AVP infusion, the ultradian rhythmic distribution of sleep and wakefulness was still present, but the amplitude of the circadian rhythm was reduced.
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PMID:Effects of chronic icv infusion of vasopressin on sleep-waking cycle of rats. 292 56

Extracellular recordings were obtained from single neurons located in the lateral septum, an area known to receive a vasopressinergic innervation in the rat brain. Approximately half of the neurons tested responded to 8-L-arginine vasopressin (AVP) by a marked increase in firing rate at concentrations greater than 1 nM. The effect of vasopressin was blocked by synthetic structural analogues possessing antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin was much less potent than vasopressin in firing septal neurons, and a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by the vasopressor agonist [2-phenylalanine,8-ornithine]vasotocin but not by the selective antidiuretic agonist 1-deamino[8-D-arginine]vasopressin. In a parallel study, sites that bind [3H]AVP at low concentration (1.5 nM) were found by in vitro autoradiography in the lateral septum. Adjacent sections were also incubated with 1.5 mM [3H]AVP and, in addition, with 100 nM [2-phenylalanine,8-ornithine]vasotocin or 1-deamino[8-D-arginine]vasopressin--i.e., the same compounds as those used for the electrophysiological study. Results showed that the vasopressor agonist, but not the antidiuretic agonist, displaced [3H]AVP, thus indicating that the vasopressin binding sites detected by autoradiography in the septum were V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. Based on the electrophysiological evidence, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurons.
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PMID:Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain. 295 62

The nature of the activity of vasopressin that is responsible for the inhibition of renin secretion was studied in normally hydrated conscious dogs using intravenous infusions of vasopressin and analogues of vasopressin with selective antidiuretic and vasoconstrictor activity. Vasopressin (1.0 ng . kg-1 . min-1) increased mean arterial pressure (MAP) from 106 +/- 2 to 115 +/- 3 mmHg (P less than 0.05) and decreased heart rate (HR) from 81 +/- 6 to 56 +/- 5 beats/min (P less than 0.001). Plasma renin activity (PRA) decreased from 4.4 +/- 1.1 to 2.4 +/- 0.8 ng . ml-1 . 3 h-1 (P less than 0.05). A specific antagonist of the vasoconstrictor activity of vasopressin, d(CH2)5MeTyrAVP (10 micrograms/kg), completely blocked the cardiovascular and renin responses to vasopressin. A selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng . kg-1 . min-1), increased MAP from 112 +/- 4 to 128 +/- 6 mmHg (P less than 0.001) and decreased HR from 69 +/- 3 to 47 +/- 4 beats/min (P less than 0.001). PRA decreased from 5.5 +/- 1.1 to 2.7 +/- 0.2 ng . ml-1 X 3 h-1 (P less than 0.001). In contrast, a selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng . kg-1 . min-1) did not alter PRA, MAP, or HR. These results demonstrate that the acute inhibition of renin secretion by vasopressin in normally hydrated conscious dogs is due to vasoconstrictor rather than antidiuretic activity.
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PMID:Role of the vasoconstrictor and antidiuretic activities of vasopressin in inhibition of renin secretion in conscious dogs. 351 May 66

The nature of the activity of vasopressin which is responsible for the inhibition of renin secretion was studied by comparing the effects of vasopressin (AVP) and analogs of AVP in anesthetized water-loaded dogs. Infusion of AVP (1.0 ng/kg/min) increased mean arterial pressure (MAP) and decreased heart rate (HR) and free water clearance (CH2O). Plasma renin activity (PRA) decreased from 11.9 +/- 4.7 to 3.8 +/- 1.7 ng/ml/3 hr (p less than 0.05). A selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng/kg/min), which had no effect on MAP or HR but was effective as AVP in decreasing CH2O, decreased PRA from 13.5 +/- 4.6 to 7.0 +/- 2.9 ng/ml/3 hr (p less than 0.05). Infusion of a selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng/kg/min), increased MAP and decreased HR but did not decrease CH2O or PRA. A vasoconstrictor antagonist, d(CH2)5Tyr(Me)AVP (10 micrograms/kg), completely blocked the MAP and HR responses to AVP but did not block the decrease in CH2O or PRA (5.9 +/- 1.8 to 2.9 +/- 1.6 ng/ml/3 hr) (p less than 0.001). Infusion of the 0.45% saline vehicle had no significant effect on MAP, HR, CH2O or PRA. These results indicate that the inhibition of renin secretion by vasopressin in anesthetized water-loaded dogs is due to its antidiuretic activity.
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PMID:Role of antidiuretic activity in the inhibition of renin secretion by vasopressin in anesthetized dogs. 352 May 11

Arginine vasopressin (AVP) is known to produce increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) and decreases in heart rate (HR), cardiac output (CO), and plasma renin activity (PRA). Some recent observations with AVP and synthetic analogues have suggested that under certain conditions, AVP can induce cardiovascular and reninsecretory responses in the opposite directions. To characterize the receptors mediating these responses, the effects of AVP, oxytocin, and synthetic neurohypophyseal analogues with specific antidiuretic, vasoconstrictor, or oxytocic activities were studied in conscious dogs. AVP and 2-phenylalanine-8-ornithine-oxytocin (Phe2Orn8OT, a selective vasoconstrictor agonist) produced similar responses when infused at 10 ng X kg-1 X min-1. That is, TPR and MAP increased, and CO, HR, and PRA decreased. Pretreatment with a selective vasoconstrictor antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid) 2-(O-methyl)tyrosine]AVP, abbreviated d(CH2)5Tyr(Me)-AVP (10 micrograms/kg), blocked the actions of Phe2Orn8OT. However, in the presence of d(CH2)5Tyr(Me)AVP, AVP actually decreased TPR and increased CO, HR, and PRA. An analogue with selective antidiuretic activity, 4-valine-8-D-AVP (VDAVP, 10 ng X kg-1 X min-1), produced the same effects as the combination of vasopressin plus d(CH2)5Tyr(Me)AVP. Neither the effects of VDAVP nor of AVP plus antagonist were blocked by propranolol (1 mg/kg). These data indicate that vasopressin, by its antidiuretic activity, produces cardiovascular effects that are opposite to many of those produced by its vasoconstrictor action and that these effects are not dependent on mediation by beta-adrenoceptors.
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PMID:Hemodynamic effects of neurohypophyseal peptides with antidiuretic activity in dogs. 384 Jun 55

There is now increasing evidence that both oxytocin (OT) and prostaglandin (PG) play a role in term as well as preterm labor. OT stimulates myometrial contractions and uterine PG release. Specific OT antagonists, therefore, may be of value in the treatment of preterm labor. Recently, we have synthesized two highly potent OT antagonists, [1-penicillamine, 4-threonine]OT ([Pen1, Thr4]OT) and [1-penicillamine, 2-phenylalanine, 4-threonine]OT ([Pen1, Phe2, Thr4]OT). We have determined their antioxytocic activity in 21- to 22-day-pregnant rats and on isolated human myometrial strips obtained from term pregnant patients at caesarean section for childbirth. We also studied their effects on PG synthesis and OT-stimulated PG synthesis on uterine slices from pregnant rats. We found that the two OT antagonists were effective inhibitors of the OT responses in pregnant rats and on pregnant human myometrial strips. The two OT antagonists had no agonistic activity on PG release at a dose range that was antioxytocic. When administered together with OT, the PG-releasing action of OT was inhibited. Thus, [Pen1, Thr4]OT and [Pen1, Phe2, Thr4]OT are effective inhibitors of both the uterotonic and PG-releasing actions of OT. The potentials of OT antagonists as tocolytic agents for the treatment of preterm labor should be explored.
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PMID:Antioxytocic and antiprostaglandin-releasing effects of oxytocin antagonists in pregnant rats and pregnant human myometrial strips. 695 12

The biological activity of peptide hormones and analogues depends on the structural and conformational properties of these compounds. A comparative study of the conformational properties of diastereoisomeric analogues of oxytocin with weak agonist activities (fully active but low potency), partial agonist activity (only able to partially induce biological response), and of conformationally restricted 1-penicillamine analogues with potent antagonist activity (no intrinsic activity, but can block the hormone's activity) was made using circular dichroism and laser Raman spectroscopies. Conformational information regarding the peptide amide, disulfide, and tyrosine chromophores was obtained, and indicates differences in the hormone agonists and antagonists. The diastereoisomeric oxytocin analogues [1-hemi-D-cystine]-, [2-D-tyrosine]-, and [5-D-asparagine]-oxytocin, have spectral features consistent with overall backbone conformations similar to oxytocin itself, but with differences in side chain moieties. This suggests that the substantial decrease in potency of the diastereoisomeric oxytocin analogues is due to changes in the relative orientations of the side chains. In contrast, the 1-penicillamine analogues of the present study, [1-penicillamine, 4-threonine]- and [1-penicillamine, 2-phenylalanine, 4-threonine]-oxytocin, like 1-penicillamine oxytocin analogues previously examined, have different backbone and disulfide conformations than oxytocin. All the 1-penicillamine oxytocin derivatives thus far examined appear, from laser Raman and CD data, to have similar topologies. However, those of the present study seem to have more rigid conformations as evidenced by very intense amide n-pi* and tyrosine pi-pi* CD transitions.
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PMID:Conformational comparisons of oxytocin agonists, partial agonists, and antagonists using laser Raman and circular dichroism spectroscopy. Examination of 1-penicillamine and diastereoisomeric analogues. 706 72


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