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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropeptides arginine vasopressin and oxytocin are generated from their prohormones in the hypothalamoneurohypophysial system by enzymatic cleavages at paired basic residues (i.e. Lys-Arg). This study describes the purification of an enzyme from bovine neural lobe secretory vesicles, the putative site of this processing, which is capable of cleaving several prohormones at paired basic residues. The enzyme is a glycoprotein of Mr approximately 70,000 and has an acidic pH maximum. It processes the heterologous precursors pro-opiomelanocortin and insulin at paired basic residues in a manner similar to a pro-opiomelanocortin-converting enzyme derived from bovine intermediate lobe secretory vesicles which has been described previously. In addition, the neural lobe-derived converting enzyme cleaves the human vasopressin prohormone in vitro to yield arginine vasopressin-Gly10-Lys11-Arg12 as the major vasopressin cleavage product. This indicates that the enzymatic cleavage in the vasopressin precursor occurred primarily on the carboxyl side of the arginine in the pair of Lys-Arg basic residues separating the vasopressin peptide from the neurophysin moiety in the precursor. The properties of the neural and intermediate lobe-derived enzymes are virtually identical, raising the possibility that a family of similar enzymes may be responsible for cleaving a number of prohormones at paired basic residues in different tissues.
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PMID:Purification and characterization of a paired basic residue-specific prohormone-converting enzyme from bovine pituitary neural lobe secretory vesicles. 302 39

The neurohypophysial hormones oxytocin (OT) and vasopressin (VP) are involved in the regulation of the contractility of the male genital tract in several animal species. We investigated the presence of specific binding sites for [3H]OT and [3H]arginine VP (AVP) in membranes prepared from tunica albuginea, epididymis, and vas deferens from prepubertal pigs 2-16 weeks of age. Membranes were incubated with [3H]OT and [3H]AVP in the presence or absence of the corresponding unlabeled peptides. Binding equilibrium was reached in 60 min at 22 C. Millimolar concentrations of Mg2+ increased the specific binding of both ligands. Analysis of families of self- and cross-displacement curves using the computer program LIGAND clearly demonstrated that two classes of binding sites were present in all tissues investigated. The first class of sites, designated the OT site, shows high affinity for OT, AVP, lysine vasopressin, arginine vasotocin, the selective OT agonists [Thr4,Gly7]OT and [Asu1,6]OT, and the OT antagonists derived from ornithine vasotocin (OVT), namely d(CH2)5Tyr(Et)OVT and dEt2OVT. The second class of sites, designated the VP site, shows high affinity for AVP, lysine vasopressin, arginine vasotocin, and the selective V1 antagonist d(CH2)5Tyr(Me)AVP. The V2 agonist [1-deamino,4-valine]8-D-AVP shows low affinity for both sites. Isotocin, desglycinamide [Arg-8]AVP and tocinoic acid were ineffective in displacing [3H]AVP or [3H]OT. The highest density of OT receptors was found in tunica albuginea and epididymis, whereas the highest density of AVP receptors was found in vas deferens. Adenylate cyclase was not activated in any of the tissues studied by concentrations of AVP or OT up to 100-fold greater than their Kd values. This is the first demonstration and pharmacological characterization of specific OT and V1 VP receptors in the tunica albuginea, epididymis, and vas deferens. The recent demonstration of high local concentration of neurohypophysial hormones in the gonads of several mammals support a physiological role of these OT and VP receptors in regulation of the motility of the male genital tract.
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PMID:Identification and characterization of two classes of receptors for oxytocin and vasopressin in porcine tunica albuginea, epididymis, and vas deferens. 302 94

WRK 1, a cloned cell line derived from a rat mammary tumour, carries specific vasopressin-binding sites. Specific binding of 2-tyrosine-3H-labelled [8-lysine]vasopressin ([3H]vasopressin) was time-dependent, saturable and reversible. Scatchard-plot analysis of hormone binding indicated the presence of a single class of receptors with an equilibrium dissociation constant of 12.7 +/- 0.2 nM. The maximal binding capacity was 75 +/- 6 fmol/10(6) cells, which corresponds to approx. 45,000 sites per cell. Oxytocin and a highly potent oxytocin analogue were able to inhibit completely [3H]vasopressin binding, but, in this respect, they were far less potent than vasopressin. This clearly demonstrates the vasopressinergic nature of this receptor. Pharmacological studies using a series of 14 vasopressin or oxytocin analogues indicated that the ligand selectivity of the vasopressin receptor found on WRK 1 cells resembles that of the rat hepatocyte. This signifies that this vasopressin receptor is of the V1a subtype. This conclusion was confirmed by the observation that vasopressin did not influence the production of intracellular cyclic AMP in WRK 1 cells.
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PMID:Characterization of specific V1a vasopressin-binding sites on a rat mammary-tumour-cell line. 303 Feb 77

Carp (Cyprinus carpio) liver maintained normal glycogen content and enzyme complement for several days in organ culture. Epinephrine-stimulated glycogenolysis, phosphorylase activation, and cyclic AMP (cAMP) accumulation in a concentration-dependent manner with EC50s of 100, 100, and 500 nM, respectively. These actions were blocked by the beta-adrenergic antagonist, propranolol, but not by the alpha-adrenergic antagonist phentolamine. Glycogenolysis and tissue cAMP were uninfluenced by 10(-6) M arginine vasotocin, arginine vasopressin, lysine vasotocin, lysine vasopressin, mesotocin, or oxytocin, but were slightly increased by 10(-5) M isotocin and slightly decreased by 10(-6) M angiotensin II. [125I]-iodocyanopindolol (ICP), a beta-adrenergic ligand, bound to isolated carp liver membranes with a KD of 83 pM. Maximum binding of 45 fmol/mg protein was at 600 pM. Propranolol, isoprenaline, epinephrine, phenylephrine, norepinephrine, and phenoxybenzamine displaced ICP with KDs of 100 nM, 2, 20, 20, 60, and 200 microM, respectively. The alpha-adrenergic antagonists, yohimbine and prazosin, showed no specific binding. These data provide evidence that catecholamines act via beta-adrenergic receptors in carp liver and that alpha-adrenergic receptors are not present. Vasoactive peptides play no significant role in regulation of carp liver glycogenolysis.
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PMID:Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio. 303 3

The binding characteristics of [3H]oxytocin [( 3H]OT) and [3H]lysine vasopressin [( 3H]LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas [3H]OT was found to bind to a single class of sites with high affinity [Kd, 1.5 +/- 0.4 (+/- SEM) nM] and low capacity [maximum binding (Bmax), 34 +/- 6 fmol/mg protein], [3H]LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for [3H]OT and [3H]LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for [3H]LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin.
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PMID:Oxytocin and vasopressin: distinct receptors in myometrium. 303 5

The primary structures of the precursors of neurohypophysial hormones vasotocin (VT) and mesotocin (MT) in the hypothalamus of the toad Bufo japonicus were determined by analyzing the nucleotide sequences of the cloned cDNAs encoding them. The MT precursor consists of 125 amino acid residues containing a signal peptide followed directly by MT, which in turn is connected to the MT neurophysin by Gly-Lys-Arg, a processing and carboxyl-terminal amidation signal. In contrast, the VT precursor includes a glycoprotein of 36 amino acids following the VT neurophysin. Except for glycoprotein, the structures of MT and VT precursors are quite similar. RNA transfer blotting analysis showed that both MT and VT mRNAs are present in the brain but not in the liver, ovaries, and testes of the toad. The sequences and the structural organizations of the MT and VT precursors are highly homologous to those of their mammalian counterparts, oxytocin and arginine vasopressin precursors, respectively. This fact suggests that, in the evolutionary pathway of neurohypophysial hormones, VT is the ancestor molecule of vasopressin, while MT is that of oxytocin.
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PMID:Cloning and sequence analysis of cDNAs for neurohypophysial hormones vasotocin and mesotocin for the hypothalamus of toad, Bufo japonicus. 303 76

The observation that suckling evokes a modest rise in serum TSH when compared with that of prolactin is inconsistent with the hypothesis that TRH serves as a hypophysiotropic mediator of this response. In the present study we attempted to provide an explanation for this discrepancy by determining whether any of a growing number of putative prolactin releasing factors could alter pituitary responsiveness to TRH. Anterior pituitaries from lactating (day 14) rats were monodispersed with trypsin, cultured for 2 days, and then incubated in the presence of medium alone or medium containing TRH, dopamine, or a combination of these secretagogues. Companion sets of cultures were incubated concurrently with either beta-endorphin, neurotensin, oxytocin, serotonin, vasoactive intestinal polypeptide, or lysine vasopressin. As expected, TRH stimulated and dopamine suppressed prolactin release. None of the substances tested except oxytocin had a significant effect on pituitary cell responsiveness to TRH or dopamine. Oxytocin had no effect on prolactin secretion when tested alone or in combination with TRH and dopamine. TRH alone stimulated TSH release by these cultures, while oxytocin and dopamine were ineffective by themselves. However, TSH secretion by cultures treated simultaneously with TRH and oxytocin could be suppressed to approximately half of that released by cells incubated with TRH alone. These results demonstrate that oxytocin attenuates TRH-induced TSH release by a direct action on pituitary cells without affecting the prolactin response. This selectivity of responsiveness imparted by oxytocin might contribute to the blunted release of TSH after suckling.
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PMID:Oxytocin attenuates TRH-induced TSH release from rat pituitary cells. 315 75

The biosynthesis and posttranslational processing of arginine vasopressin (AVP) and oxytocin (OT) peptides in the developing rat brain and pituitary were studied using antibodies and complementary separation methods that permitted a quantitative radioimmunoassay (RIA) analysis of precursor, intermediate, and completely processed forms of the peptides. Precursor forms of the peptides were first detected in rat brain as early as embryonic day (E) 15 for AVP and E17 for OT. Proteolytic cleavage products of the precursors were detected 1 d later for both peptides. AVP was present in a fully processed (amidated) from immediately (E16) and throughout fetal development. OT was cleaved from its precursor starting on E18 but remained in an intermediate (C-terminal extended) form until E21, when amidated OT was first detected in the pituitary. Hence, Pro-AVP processing in the fetus was immediate and complete, whereas Pro-OT processing in the fetus was much slower and incomplete, resulting in the generation of partially processed, nonamidated stable forms of the peptide (OT-Gly10, OT-Gly10-Lys11, and OT-Gly10-Lys11-Arg12). The presence of OT-Gly10-Lys11-Arg12 as a major, stable intermediate form, indicated that the in vivo pattern of endoproteolytic cleavage occurred principally at the C-terminus of the pair of basic amino acids at the tripeptide spacer sequence (Gly-Lys-Arg) in the precursor. Although both precursors were first expressed nearly simultaneously in the brain, the steady-state levels of the precursors were very different throughout fetal life. From E16-E21, the quantities of AVP precursors and peptides were 5- to 10-fold greater than those of OT, suggesting a much higher level of precursor biosynthesis in the AVP neurons. In addition to these differences in the regulation of biosynthesis and processing, AVP peptides were axonally transported to the pituitary 3 d earlier than OT peptides, and in far greater (20-fold) abundance. The early presence and abundance of amidated AVP in the brain and pituitary suggests a trophic function for this peptide during development.
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PMID:Differential biosynthesis and posttranslational processing of vasopressin and oxytocin in rat brain during embryonic and postnatal development. 318 9

Local endometrial blood flow was measured by a thermistor technique and myometrial activity by intrauterine pressure recording in 10 women before and during menstruation. The effect of lysine vasopressin infusion (1 pmol/kg body-weight per min) and of bolus injection of a synthetic oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (10 nmol/kg body-weight), were studied. Spontaneous variations in blood flow were seen synchronous with clearly demarcated uterine contractions, the myometrial activity being significantly increased in early (day -1 to day +2) compared with late (day +3 to day +5) menstrual phase. The vasopressin infusion decreased blood flow, stimulated uterine activity and caused slight to moderate dysmenorrhoea-like pain. These effects were completely inhibited by the injection of the oxytocin analogue. In-vitro studies on uterine arteries confirmed that the analogue also inhibited the vasopressin-induced constriction of the uterine arteries. This antagonist was more effective than two other analogues, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-oxytocin and 1-deamino-2-Tyr(OEt)-oxytocin. The counteracting effect of 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin on the vasopressin-induced decrease of blood flow and increase of contractions supports the therapeutic value of the drug in primary dysmenorrhoea and preterm labour.
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PMID:Uterine blood flow and myometrial activity at menstruation, and the action of vasopressin and a synthetic antagonist. 319 Oct 63

The neurohypophyseal hormones of the hippopotamus (Hippopotamus amphibius) and collared peccary (Tayassu angulatus) were isolated by molecular sieving and preparative high-pressure liquid chromatography (HPLC). Oxytocin and arginine vasopressin have been identified by their amino acid compositions and their retention times in HPLC. Lysipressin (lysine vasopressin) was not detected in posterior pituitaries of two hippopotami and nine peccaries (less than 2% of arginine vasopressin in molar ratios). Among the suborder Suiformes of Artiodactyla, the families Hippopotamidae and Tayassuidae do not seem to possess lysipressin, in contrast to the family Suidae in which the pig has lysipressin in place of arginine vasopressin.
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PMID:The distribution of lysine vasopressin (lysipressin) in placental mammals: a reinvestigation of the Hippopotamidae (Hippopotamus amphibius) and Tayassuidae (Tayassu angulatus) families. 319 70


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