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)

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

Optimized C18 reversed-phase systems for oxytocin, desamino-oxytocin, lysine-vasopressin, ornithine-vasopressin and felypressin with gradient elution are discussed, focussing on precision, selectivity and ruggedness of the methods. Data from collaborative studies are presented, demonstrating the equivalence of high-performance liquid chromatography (HPLC) assays to bioassays. The findings suggest that HPLC is an excellent alternative to the time-consuming and less reliable animal testing.
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PMID:The use of high-performance liquid chromatography in the quality control of oxytocin, vasopressin and synthetic analogues. 248 22

To investigate whether a putative oxytocin (OT) receptor blocker 1-deamino-[2-D-tyrosine (OEt)-4 threonine-8-ornithine]oxytocin (dTVT) inhibits OT binding to its receptors, we studied binding of [3H]OT to late-pregnant human, guinea pig, and rat myometrial and decidual membranes and competition of dTVT with this binding. Decidua as well as myometrium of all three species bound [3H]OT with high affinity (Kd 1-3 nM) and limited capacity. The concentration of binding sites in decidual membranes was slightly lower than in myometrial membranes in human and guinea pig uterus and twice that of myometrial membranes in day 20 pregnant rat uterus. dTVT competed with [3H]OT with highest affinity in guinea pig myomterium and decidua, the potency ratios ([dTVT]50: [OT]50) being 1.9 and 3.3, respectively. The potency ratios in rat uterine tissues and human decidua were slightly higher (4 to 5) and highest in human myometrium, 23.3. Excess dTVT completely inhibited [3H]OT binding in all six tissues, indicating binding to the same receptor sites. Because of the high-affinity binding of dTVT to oxytocin receptors in human decidua and myometrium, this oxytocin analogue may be a very effective tocolytic agent in the treatment of threatened preterm labor.
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PMID:Oxytocin antagonist (dTVT) and oxytocin receptors in myometrium and decidua. 254 Jul 61

Saturation analysis and competition experiments were performed to identify and characterize [3H]arginine vasopressin binding to human myometrium and decidua in late pregnancy. [3H]Arginine vasopressin bound with affinity similar to that of [3H]oxytocin to both tissues (dissociation constant 1 to 2 nmol/L). The concentration of [3H]arginine vasopressin binding sites was high, particularly in decidua, but in all instances was about 50% to 60% of [3H]oxytocin binding. Analogs with selective oxytocic potency (4-threonine oxytocin, isotocin) had high affinity to both [3H]arginine vasopressin and [3H]oxytocin binding sites, as did analogs with both oxytocic and vasopressor activity (vasotocin). Analogs with selective antidiuretic activity (1-deamino-8-D-arginine vasopressin) showed drastically reduced affinity to [3H]oxytocin binding sites and relatively low but significantly higher affinity to [3H]arginine vasopressin binding sites. A new oxytocin antagonist (RW22164 or [1-deamino-2D-tyrosine-(O-ethyl)-4-threonine-8-ornithine]oxytocin) competitively bound to both binding sites. Its affinity to [3H]oxytocin binding sites was greater than to [3H]arginine vasopressin binding sites whereas the relative affinities of a predominantly vasopressor antagonist [Manning compound) were reversed, suggesting the presence of distinct receptors for oxytocin and arginine vasopressin in pregnant human myometrium and decidua.
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PMID:Vasopressin receptors in human pregnant myometrium and decidua: interactions with oxytocin and vasopressin agonists and antagonists. 255 63

An oxytocic antagonist, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid,2-O-methyltyrosine,4-threonine, 8-ornithine,9-tyrosylamide]vasotocin (d(CH2)5[Tyr(Me)2, Thr4,Tyr-NH2(9)]OVT [corrected], was monoiodinated at the phenyl moiety of the tyrosylamide residue at position 9. 125I-labelling was performed with 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenyl-glycoluril. Iodination resulted in an increased affinity for rat uterine oxytocin receptors. A considerably lower affinity for rat vascular V1- and renal V2-receptors was found, resulting in a highly specific oxytocin receptor ligand. 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT [corrected] was demonstrated to bind selectively to one population of binding sites in rat uterus and ventral hippocampal membrane preparations. Dissociation constants ranged between 0.03 and 0.06 nM. After 3 days of exposure autoradiography revealed binding in regions known to contain oxytocin receptors as well as labelling in some new regions, while no binding was found in the lateral septum, a structure containing mainly [8-arginine]vasopressin receptors. The high specific radioactivity of 125I-labelling allowed important reductions in membrane protein amount, gain in precision of binding analysis as well as considerably lower exposure times for autoradiography.
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PMID:125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT: a selective oxytocin receptor ligand. 283 49

A new, highly selective radio-iodinated oxytocin receptor antagonist [( 1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid, 2-O-methyltyrosine, 4-threonine, 8-ornithine, 9-tyrosylamide]-vasotocin) was used to identify and quantitate specific binding sites for the neurohypophyseal hormone oxytocin with in vitro incubation of rat brain sections and autoradiography. Exclusively oxytocin binding sites were detected in view of the high affinity of the [125I]-labelled oxytocin antagonist for oxytocin binding sites and the negligible affinity for the vasopressin liver (V1) and kidney (V2) receptor types. The putative oxytocin receptors were abundantly present in several brain regions, where previously discrimination between oxytocin and vasopressin binding was difficult, i.e. the olfactory nucleus, the islands of Calleja, the ventromedial nucleus of the hypothalamus, the central amygdaloid nucleus and the ventral subiculum of the hippocampus. In addition oxytocin receptors were demonstrated in other areas, such as the taenia tecta, dorsolateral caudate putamen, ventral pallidum, accumbens, lateral septum, bed nucleus of the stria terminalis, thalamic paraventricular nucleus, lateral, basolateral and medial amygdala, the dorsal subiculum, perirhinal cortex and the amygdaloid-hippocampal area. The high affinity and the low detection threshold of this [125I]-labelled oxytocin antagonist permitted identification of oxytocin receptors in new regions such as the ventral part of the lateral septum, medial septum, dorsal motor nucleus of the vagus nerve and the olive nuclei in the brain stem.
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PMID:Topography of the oxytocin receptor system in rat brain: an autoradiographical study with a selective radioiodinated oxytocin antagonist. 285 12

The sensitivity of the mouse anococcygeus to contraction by oxytocin was shown to be Mg2+-dependent. Decreasing [Mg2+]0 from the optimal concentration of 1 to 0 mM caused a 20-fold parallel rightward displacement of the oxytocin dose-response curve. Contractions to oxytocin-related peptides (Arg-vasotocin, Arg-vasopressin and Lys-vasopressin) were also Mg2+-dependent, but those to other drugs (carbachol, methoxamine and thyrotrophin releasing hormone) were not. The onset of the potentiating effect of Mg2+ was rapid, full potentiation occurring within 70 s. 1-Deaminopenicillamine 8-ornithine-vasotocin produced competitive antagonism of responses to oxytocin, but was more potent in the absence (pA2 = 8.01) than in the presence of Mg2+ (1 mM; pA2 = 7.52). Thus, physiological concentrations of [Mg2+]0 enhanced oxytocin agonist potency but decreased oxytocin antagonist potency; possible mechanisms are discussed.
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PMID:Magnesium ions and oxytocin sensitivity of the male mouse anococcygeus. 286 97

We describe the synthesis and some pharmacological properties of 16 new in vivo antagonists of oxytocin. These are based on modifications of three peptides: A, B, and C. A is our previously reported potent and selective antagonist of the vasopressor (V1 receptor) responses to arginine-vasopressin (AVP)/weak oxytocin antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid), 2-O-methyltyrosine]arginine-vasopressin (d(CH2)5[Tyr(Me)2]AVP. B reported here, the Ile3 analogue of A, is d(CH2)5[Tyr(Me)2]AVT (5 below) and C is our previously reported potent nonselective oxytocin antagonist/AVP V1 antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O- methyltyrosine,8-ornithine]vasotocin (d(CH2)5[Tyr(Me)2]OVT). The following substitutions and deletions, alone or in combination, were employed in A, B, and C: 1-deaminopenicillamine (dP); D-Tyr(Alk)2 (where Alk = Me or Et), D-Phe2; Val4, Thr4; delta 3-Pro7; Lys8, Cit8; desGly9, desGly-NH2(9), Ala-NH2(9); Leu-NH2(9); Arg-NH2(9). The 16 new analogues are (1) d(CH2)5[D-Tyr(Me)2]AVP, (2) d(CH2)5[D-Tyr(Me)2, Val4,delta 3-Pro7]AVP, (3) d(CH2)5[D-Tyr-(Et)2, Val4,Lys8]VP, (4) d(CH2)5[D-Tyr(Et)2,Val4,Cit8]VP, (5) d(CH2)5[Tyr(Me)2]AVT, (6) d(CH2)5[Tyr(Me)2,Lys8]VT, (7) dP[Tyr(Me)2]AVT, (8) dP[Tyr(Me)2,Val4]AVT, (9) d(CH2)5[D-Tyr(Me)2, Val4]AVT, (10) d(CH2)5[D-Phe2,Val4]AVT, (11) d(CH2)5[Tyr(Me)2,Thr4]OVT, (12) d(CH2)5[Tyr(Me)2,Thr4,Ala-NH2(9)]OVT, (13) d(CH2)5[Tyr(Me)2,Thr4,Leu-NH2(9)]OVT, (14) d(CH2)5[Tyr(Me)2,Thr4,Arg-NH2(9)]OVT, (15) desGly-NH2(9),d(CH2)5[Tyr(Me)2,Thr4]OVT, (16) desGly9,d(CH2)5[Tyr(Me)2,Thr4]OVT. 1-4 are analogues of A, 5-10 are analogues of B, and 11-16 are analogues of C. Their protected precursors were synthesized either entirely by the solid-phase method or by a combination of solid-phase and solution methods (1 + 8 or 8 + 1 couplings). All analogues were tested in rats for agonistic and antagonistic activities in oxytocic (in vitro, without and with Mg2+, and in vivo) assays as well as by antidiuretic and vasopressor assays. All analogues exhibit potent oxytocic antagonism in vitro and in vivo. With an in vitro pA2 (in the absence of Mg2+) = 9.12 +/- 0.09, dP[Tyr(Me)2]AVT is (7) one of the most potent in vitro oxytocin antagonists reported to date. Fifteen of these analogues (all but 6) appear as potent or more potent in vivo oxytocin antagonists than C (pA2 = 7.37 +/- 0.17). Analogues 1-9 and 14 are potent AVP V1 antagonists. Their anti-V1 pA2 values range from 7.92 to 8.45. They are thus nonselective oxytocin antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Solid-phase synthesis of 16 potent (selective and nonselective) in vivo antagonists of oxytocin. 291 98

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

Neurohypophysial hormones stimulate the motility of tunica albuginea, epididymis, and vas deferens acting through oxytocin (OT) and V1 vasopressin receptors. To test the hypothesis that these hormones are involved also in the regulation of seminal vesicle physiology, we studied binding of [3H]OT and [3H] arginine vasopressin ([3H]AVP) to porcine seminal vesicle membranes. Neurohypophysial hormones bind to two different classes of sites. The first class shows low capacity (35 fmol per mg of protein) and a very high affinity (Kd less than 1 nM) for both the labeled ligands. The second class is characterized by a high capacity (2000 fmol per mg of protein) and a high affinity for AVP (Kd approximately equal to 2.5 nM), whereas OT has 160 times lower affinity. Lysine vasopressin and the V1 antagonist [1-deaminopenicillamine, 2-(O-methyl)tyrosine]Arg8-vasopressin compete with high affinity with [3H]AVP binding, whereas the V2 agonist [1-deamino,4-valine]D-Arg8-vasopressin (dVDAVP) is 110 times less potent than AVP. The OT agonist [Thr4,Gly7]OT and the OT antagonist [1(beta-mercapto-beta, beta-cyclopentamethylene propionic acid), 2-(O-ethyl)tyrosine, 8-ornithine]vasotocin failed to affect [3H]AVP binding. These findings seem to suggest that AVP interacts with the V1 vasopressin isoreceptor in porcine seminal vesicle membranes. However, AVP stimulates adenylate cyclase activity in a dose-dependent fashion with an EC50 of 14 nM, whereas OT or dVDAVP has no effect at 100 nM. Moreover, a well-characterized V1 vasopressin antagonist, [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine]Arg8-vasopressin [d(CH2)5Tyr(Me)AVP], competes with [3H]AVP binding with an IC50 of 0.17 microM. These pharmacological properties are distinct from the previously described V1 and V2 vasopressin receptors and indicate the presence of a new class of AVP receptors. Although this vasopressin isoreceptor shares some pharmacological characteristics with the V1 (pressor) isoreceptor, it has low affinity for the V1 antagonist d(CH2)5-Tyr(Me)AVP and is linked to the adenylate cyclase system. The extremely high density of AVP receptors in porcine seminal vesicles (2 pmol per mg of protein) is comparable to the density of V2 vasopressin receptors in porcine renal medulla, suggesting a physiological role for vasopressin in the seminal vesicle.
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PMID:Identification and characterization of a vasopressin isoreceptor in porcine seminal vesicles. 294 37


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