UNIPROT:P01178 - FACTA Search

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

The present paper deals with the development of an immunofluorescence procedure that allows specific localization of vasopressin and oxytocin in the hypothalamo-neurohypophyseal system(hnx) of the rat. Antibodies against arginine vasopressin (AVP), lysine-vasopressin (LVP) and oxytocin were raised by injecting these hormones that were covalently bound to thyroglobulin into rabbits. The vasopressin-immunized rabbits showed periods of diabetes insipidus, while histoloty of the "hns revealed an intact neurosecretory system with signs of increased endogenous hormone synthesis in the supraoptic nucleus and increased release in the neuro-hypophysis of some rabbits. The daily water intake of the oxytocin-immunized rabbits was similar to that of control rabbits. The development of antibodies against vasopressin as measured in the immunofluorescence procedure showed a course that was quite different from the curve of the titer as determined by radioimmunoassay (RIA). Also the specificity of the antibodies used in the immunofluorescence procedure was found to be quite different from their specificity in a RIA system. Potency and specificity of the antibodies have to be studied therefore within the immunofluorescence procedure itself. Using freshly frozen acetone-postfixed hypotalami or pituitaries, no sharp localization of immunofluorescence could be obtained in the HNS. Therefore prefixation was performed. Both, the type and the duration of prefixation revealed quite different results regarding the immunofluorescence in the neurosecretory cell boides in the hypotalamus and of their endings in the neurohypophysis. The best immunofluorescence results were obtained using 6 hours glyoxal-prefixation for the hypothalamus and 24 hours formalin-prefixation for the pituitary. The cross-reaction of the antibodies for oxytocin or vasopressin was tested on synthetic hormones that were bound to CNBR-activated agarose beads and mounted on glass sides. All anti-plasmas showed cross-reaction on beads containing the heterologou- antigen. The plasmas were purified by incubation with beads containing the heterologous hormone until the cross-reacting component had been removed. Using purified antibodies, the distribution of oxytocin and vasopressin cells within the HNS was investigated. More oxytocin containing cells were localized in the rostral part and more vasopressin in the caudal part of both, the supraoptic (SON) and paraventricular nucleus (PVN). Comparable percentages of oxytocin and vasopressin containing cells were found in the SON and PVN. The absolute amount of oxytocin containing cells was 2.5 times more in the SON than in the PVN, which seems to contradict the "classical" view that the PVN predominantly or entirely synthetizes oxytocin. In addition, fluorescence was found using antobodies against vasopressin in the suprachiasmatic nucleus in Wistar rats and heterozygous Brattleboro rats, but not in this nucleus of homozygous Brattleboros.
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PMID:Immunofluorescence of vasopressin and oxytocin in the rat hypothalamo-neurohypophypopseal system. 110 Jul 84

Arginine-vasopressin and oxytocin, both 14C-labeled in the glycine residue, are enzymatically inactivated by rat kidney supernatant. Production of radioactive metabolites of each hormone was followed as a function of time. Both oxytocin and vasopressin are degraded by an enzyme which cleaves their Pro-X bonds, to release Leu-Gly-NH2 from oxytocin and Arg-Gly-NH2 from vasopressin. In addition, oxytocin alone is degraded rapidly by a chymotrypsin-like enzyme which directly releases Gly-NH2 from the hormone. The direct release of Gly-NH2 from vasopressin in the homogenate is of minor importance, but there occurs a transient formation of an uncharacterized fragment in significant amounts. The data are interpreted to indicate that the difference in the overall mechanism of inactivation of the two hormones by the rat kidney extract is a result of the high level of the enzymic activity which releases Gly-NH2 directly from oxytocin, compared to the low level of activity releasing Gly-NH2 directly from the antidiuretic hormone. This allows, in the case of arginine vasopressin, a greater expression of the activity of enzyme(s) giving rise to uncharacterized fragment(s) and of the Pro-X cleaving enzyme.
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PMID:Differences in the enzymatic inactivation of arginine vasopressin and oxytocin by rat kidney homogenate. 111 88

Subcommissural organs of young and mature rabbits were analyzed for their content of arginine vasotocin by radioimmunoassay. Younger animals had significantly greater quantities of this peptide. There was no detectable arginine vasopressin or oxytocin in subcommissural organ extracts. It is concluded that the subcommissural organ represents, in addition to the pineal and the fetal neurohypophysis, another significant source of arginine vasotocin in the mammalian central nervous system.
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PMID:Arginine vasotocin in the rabbit subcommissural organ. 112 Apr 69

Antibodies for the radioimmunoassay of arginine vasopressin (AVP) described here were produced in rabbits using synthetic AVP coupled to rabbit gamma-globulin with carbodiimide. In three out of six rabbits, significant antibody titres were obtained. Using the best antisera produced, 40% of labeled AVP was bound at a final dilution of 1:50.000. After iodination of synthetic AVP with 125I using the chloramin-T method, a gel filtration on Sephadex G-25 was performed to purify the iodinated AVP. For separation of antibody bound and free hormone, a second antibody precipitation was used. There was no crossreactivity with oxytocin. AVP was extracted from plasma after ammoniumsulfate precipitation of the proteins by adsorption to Florisil. The recovery of AVP added to plasma in amounts between 5-25 pg/ml was 60 +/- 15% (n equals 6). The minimum amount of AVP detectable was 1 pg per ml plasma. The plasma level in normal adults under standard conditions was 3.4 +/- 2.2 pg/ml. This is in agreement with data recently published by other researchers. The applicability and reproducibility was further tested in measurements of samples taken hourly during the entire day under water diuresis and after hormonal stimulation of AVP.
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PMID:Radioimmunoassay of arginine vasopressin in human plasma. 124 86

Certain neuropeptides can facilitate lordosis by acting on midbrain periaqueductal gray (PAG) in estrogen-primed female rats. Here, we investigated responses of individual PAG neurons in vitro, to five neuropeptides: substance P (SP), luteinizing hormone-releasing hormone (LHRH), prolactin (PRL), oxytocin (OT), and thyrotropin-releasing hormone (TRH). Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way. Oxytocin acted through oxytocin receptors located on the recorded PAG neurons, since excitatory actions of OT were 1) not abolished by synaptic blockade, 2) mimicked by the OT-specific agonist [Thr4, Gly7]OT but not by arginine vasopressin, and 3) blocked by the OT-specific antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin. Although LHRH had no neurotransmitter-like action on spontaneous activity of PAG neurons, it, as well as SP, could modulate responses of some dorsal PAG neurons to GABAA and GABAB agonists or norepinephrine. Neuromodulatory actions of LHRH and SP could help facilitate lordosis through PAG neurons.
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PMID:Effects of lordosis-relevant neuropeptides on midbrain periaqueductal gray neuronal activity in vitro. 128 9

1. Extracellular recordings were made from 297 spontaneously firing neurones in the dorsal motor nucleus of the vagus (DMV) in slice preparations of rat medulla oblongata. Some of the neurones recorded were identified to be vagal motoneurones by antidromic stimulation. The cells fired with a slow irregular pattern at an average rate of 1.1 +/- 0.1 spikes/s (mean +/- S.E.M.). 2. Arginine vasopressin (AVP) was applied by perfusion in 196 of the 297 cells. Most of the neurones (190/196, 97%) were excited by 10(-6) M AVP with an increase in firing rate from the basal level of 1.1 +/- 0.1 to a maximum of 2.5 +/- 0.2 spikes/s. There was a dose-dependent relation between the concentration of AVP and the increased firing rate in all DMV neurones tested (n = 38). The threshold concentration of the peptide to produce changes in firing rate was assumed to be about 10(-10) M. The remaining six neurones were not affected by application of AVP. 3. Application of oxytocin (OXT, 10(-6) M) increased the firing rate of all thirty-eight neurones tested. The effects of AVP and OXT on all neurones examined (n = 20 and 4, respectively) still persisted after blocking the synaptic transmission in a low-Ca2+ or Ca(2+)-free-high-Mg2+ solution, indicating the direct action of both AVP and OXT on the postsynaptic membranes. 4. The AVP-induced excitatory responses were completely but reversibly blocked by the V1-type receptor antagonists, [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid), 2-(O-methyl)tyrosine]-arginine vasopressin (d(CH2)5Tyr(Me)AVP) (n = 5) and Phaa-D-Tyr(Et)Phe-Gln-Asn-Lys-Pro-Arg-NH2 (n = 6), whereas a selective and reversible OXT receptor antagonist, desGly-NH2d(CH2)5[Tyr-(Me)2Thr4]ornithine vasotocin, which suppressed the OXT-induced excitation, did not block the responses to AVP (n = 11). 5. Application of angiotensin II (AII, 10(-6) M) to 153 neurones increased the firing rates of 60 (39%) neurones. The firing rate was increased from the basal level of 1.0 +/- 0.1 to a maximum of 1.8 +/- 0.2 spikes/s (n = 60). The effect of AII was completely abolished by an AII receptor antagonist, [Sar1,Ile8]angiotensin II (n = 6). There was a dose dependence of the excitatory response on AII concentration in all of eleven neurones tested. The threshold concentration was assumed to be about 10(-9) M. The activity of 5 (3%) of 153 neurones was decreased, and the remaining 88 (58%) neurones were not affected by AII.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro. 130 79

A technique has been developed for prelabelling and permeabilisation of guinea pig uterine myocytes to enable measurement of arachidonic acid release/phospholipase A2 activity in cells with intact membranes. Intact cells were prelabelled with [3H]inositol or [3H]arachidonic acid for measurement of phospholipase C and A2 respectively. In intact cells 10 nM endothelin-1 or 1 microM bradykinin stimulated both inositol polyphosphate and arachidonic acid release, whilst 1 microM oxytocin, arginine vasopressin or histamine were without effect. In Streptolysin-O permeabilised myometrial cells calcium-stimulation of inositol polyphosphate and arachidonic acid release was detected between 10 microM and 1 mM free calcium. The patterns of inositol polyphosphate and arachidonic acid release were broadly similar. Responses to 1 mM calcium were not detected in intact cells not treated with Streptolysin-O. For arachidonic acid release the K0.5 for calcium activation was about 7 microM, a level above that normally likely to be found in the uterine myocyte. Hence it is concluded that unless there are high local concentrations of calcium close to the plasma membrane, calcium is unlikely alone to be the primary regulator of arachidonic acid release and phospholipase A2.
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PMID:Measurement of arachidonic acid release from permeabilised myometrial cells of guinea pig uterus. 130 78

In a previous report we demonstrated the presence of a vasotocin (AVT)-like peptide in chromaffin cells of the amphibian adrenal gland and showed that synthetic AVT is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells. In the present study we evaluated the relative potency of various AVT analogs and investigated the mechanism of action of AVT on frog interrenal (adrenal) tissue. Several AVT agonists, including hydrin 2, oxytocin (OXT), arginine vasopressin (AVP), Lys-conopressin G, and mesotocin (MT), were able to mimic the stimulatory effect of AVT on steroid secretion, but AVT was by far the most potent stimulator of steroidogenesis. In the series of analogs studied, the order of potency was: AVT greater than hydrin 2 greater than OXT greater than AVP greater than Lys-conopressin G greater than MT greater than [deamino-Cys1,D-Arg8]AVP greater than [d(CH2)5,Tyr(OMe)2] AVP. The effect of AVT (5 x 10(-10) M) was totally blocked by both the antidiuretic V2 antagonist [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP (10(-6) M) and the oxytocinergic antagonist [d(CH2)5,Tyr(OMe)2,Orn8]AVT (10(-6) M); the V2 antagonist was approximately twice as potent as the OXT antagonist. In contrast, the V1 antagonist 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-AVP (10(-6) M) did not affect the response of the interrenal tissue to AVT. Indomethacin (5 microM), a cyclooxygenase inhibitor, induced a dramatic decrease in the spontaneous secretion of corticosteroids, but did not impair the stimulatory effect of AVT (5 x 10(-9) M) on corticosterone and aldosterone secretion. In addition, AVT did not stimulate the production of prostaglandin E2, suggesting that prostaglandins are not involved in the mechanism of action of AVT. Concurrently, AVT did not modify cAMP production by frog adrenal slices. In contrast, AVT induced both an increase in inositolphosphate production and a reduction of membrane phospholipid content. We conclude that in the frog adrenal gland, the stimulatory effect of AVT on steroid secretion is mediated through activation of receptors related to the mammalian V2 and/or OXT receptors, which are positively coupled to phosphoinositide-specific phospholipase C.
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PMID:Pharmacological characterization of vasotocin stimulation of phosphoinositide turnover in frog adrenal gland. 130 45

Neurohypophysial hormone receptors were studied in myometrial specimens obtained from nonpregnant women using binding and in vitro contractility studies. The mathematical modeling of self- and cross-competition curves among [3H]oxytocin (OT), [3H]arginine vasopressin, the V1 vasopressin (VP) antagonist [3H]d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and the OT agonist [Thr4, Gly7] OT strongly indicates the presence of multiple classes of OT and arginine vasopressin receptors. The latter show the same pharmacological characteristics as the neurohypophysial hormone receptors described by our group for the human pregnant myometrium; in addition, they regulate the contractility of uterine strips. Blocking experiments were performed to evaluate the relative OT and V1 VP receptor distribution in 30 uterine specimens obtained from normal cycling and postmenopausal women. The glucuronoconjugate metabolites of 17 beta-estradiol and progesterone were also measured in 16 patients in early morning urine samples taken the same day as surgery. Our results show that V1 VP receptors are not only present but also biologically active in all the uterine specimens studied with virtually equal density in normal cycling and postmenopausal women. However, their concentrations do not correlate with either estrogen or progesterone urinary levels. The lowest OT receptor density was found at mid-cycle and in menopause, independently of any correlation with the urinary estrogens. Conversely, OT receptors rise sharply in the late luteal phase and during menstruation. In addition they show a positive relationship with glucuronoconjugate metabolites of progesterone levels. These results indicate that progesterone does not inhibit the expression of uterine OT receptors in the human uterus. Furthermore, they imply that neurohypophysial hormones are involved in the control of uterine activity during the menstrual cycle.
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PMID:Sex steroid modulation of neurohypophysial hormone receptors in human nonpregnant myometrium. 130 35

The potency of oxytocin (OT) in evoking ACTH secretion by isolated, superfused rat adenohypophyseal corticotrophs and its enhancement by CRF and arginine vasopressin (AVP) were analyzed. Each secretagogue effectively released ACTH from adenohypophyseal cells when added separately in pulsatile fashion in physiological concentrations based on hypophyseal portal blood (OT, 10 nM; AVP, 0.5 nM; CRF, 0.1 nM). OT released ACTH at concentrations as low as 1 nM. Moreover, a dose-response relationship up to 10 microM was revealed. Combinations of a constant amount of CRF (0.1 nM) with increasing concentrations of OT exerted a synergistic effect on ACTH release. In contrast, OT given in various concentrations in combination with AVP (0.5 nM) produced an additive effect on ACTH release. To study the mechanism of action of OT on ACTH secretion, cytosolic free calcium levels in single pituitary cells exposed to OT or AVP were measured using the calcium-sensitive fluorescent indicator Fura-2. Corticotrophs among mixed adenohypophyseal cell types in the primary cultures were identified by immunocytochemistry. More than 500 cells were individually stimulated with OT or AVP. Basal cytosolic free calcium levels ranged between 80-130 nM free calcium. The addition of 100 nM OT or 1 microM AVP increased the cytosolic free calcium concentration within 3 sec to values ranging from 500-800 nM. An increase in intracellular calcium ranging from 200-500 nM due to OT could still be observed after extracellular calcium depletion. Taken together, our data demonstrate that physiological concentrations of OT stimulate ACTH secretion, independent of the other ACTH secretagogues, by mobilizing calcium mainly from intracellular stores.
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PMID:Oxytocin at physiological concentrations evokes adrenocorticotropin (ACTH) release from corticotrophs by increasing intracellular free calcium mobilized mainly from intracellular stores. Oxytocin displays synergistic or additive effects on ACTH-releasing factor or arginine vasopressin-induced ACTH secretion, respectively. 131 49

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