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 effects of intracerebroventricularly (icv.) administered oxytocin (OXT) and lysine-8-vasopressin (LVP) on the development of hypothermic tolerance to ethanol were investigated. Mice equipped with an icv cannula were pretreated with graded doses of OXT or LVP (3 ng, 300 pg, 30 pg or 3 pg/animal) before the daily intraperitoneal ethanol (4 g/kg) injection. Two doses of OXT or LVP (3 ng or 300 pg/animal) blocked the development of hypothermic tolerance to ethanol. Smaller doses of the peptides were ineffective in inhibiting the gradual decrease in hypothermia upon repeated ethanol administration, which effect was observed in the control group. The data presented show that the central administration of these neurohypophyseal peptides blocks the development of tolerance to ethanol.
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PMID:Intraventricular administration of neurohypophyseal hormones interferes with the development of tolerance to ethanol. 271 43

Peptidyl glycine alpha-amidating mono-oxygenase (PGA), the terminal enzyme in the pathway of oxytocin synthesis, was measured in extracts of ovine corpora lutea throughout the oestrous cycle. Activity of PGA was low early in the cycle but increased between days 2 and 10 (from 2.3 to 9.0 pmol/mg protein per h) and remained high until day 15. Thereafter, activity declined rapidly at structural luteolysis and was low in corpora albicantia collected 18 and 20 days after ovulation (1.28 and 1.07 pmol/mg protein per h respectively). Luteal concentrations of ascorbic acid, a cofactor for PGA, were high (4.7 mumol/g wet wt tissue) by day 4 after oestrus; concentrations fell rapidly after day 15 (to 2.1 mumol/g on day 16). Concentrations of ascorbic acid were also high in the pituitary gland and in the adrenal medulla and cortex. Concentrations of oxytocin in luteal tissue, which were low (0.3 nmol/g wet wt) on day 2 after oestrus, were highest (2.73 nmol/g) on day 6 and declined thereafter (0.56 nmol/g on day 10, 0.08 nmol/g on day 15 and not detectable on days 18 and 20). Concentrations of oxytocin, progesterone, PGA and protein were measured in subcellular fractions obtained after density gradient centrifugation of extracts of corpora lutea collected on days 6, 7 and 12 of the oestrous cycle, and on day 7 from an anaesthetized ewe before and after treatment with the prostaglandin F2 alpha analogue, cloprostenol. PGA colocalized with particle-associated oxytocin in fractions of density 1.049-1.054 g/ml. Exogenous [3H]oxytocin and [3H]progesterone and endogenous progesterone localized in fractions of density 1.035 g/ml. Oxytocin and PGA were depleted from fractions of density 1.049-1.054 g/ml following cloprostenol treatment in vivo. Fractionation of extracts of ovine corpora lutea by high-performance liquid chromatography (HPLC) followed by radioimmunoassay and radioreceptor assay for oxytocin demonstrated the presence of at least two cross-reacting substances with elution characteristics distinct from oxytocin. Concentrations of these peptides increased as the cycle progressed. These compounds differed from the putative C-terminally extended post-translational processing intermediates, oxytocinyl-glycine, oxytocinyl-glycine-lysine and oxytocinyl-glycine-lysine-arginine, as indicated by their elution positions on HPLC and the specificities of the assays used to detect them, and no conclusions could be drawn on which post-translational processing step was rate-limiting in oxytocin synthesis. These data are consistent with the suggestion that post-translational processing of oxytocin-neurophysin prohormone takes place in secretory granules in luteal cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Post-translational processing of oxytocin-neurophysin prohormone in the ovine corpus luteum: activity of peptidyl glycine alpha-amidating mono-oxygenase and concentrations of its cofactor, ascorbic acid. 276 55

From neurointermediate pituitary glands of Xenopus laevis and Rana esculenta, previously unreported peptides termed hydrins, active on water permeability of frog urinary bladder and frog skin (Brunn or "water-balance" effect), have been isolated and sequenced. These peptides seem to be derived from the pro-vasotocin-neurophysin precursor. Hydrin 1, found in Xenopus, has been identified as vasotocin C-terminally extended with the Gly-Lys-Arg sequence; hydrin 2, found in Rana, has been identified as vasotocin C-terminally extended with glycine. Hydrin 2 has been detected in several Ranidae (R. esculenta, Rana temporaria, Rana pipiens) and Bufonidae (Bufo bufo, Bufo ictericus) and appears to have a large distribution in terrestrial or semiaquatic anurans. Hydrins, in contrast to vasotocin, are not active on rat uterus or rat blood pressure. They are absent from other vasotocin-bearers such as birds and could be involved specifically in water-electrolyte regulation of amphibians.
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PMID:Hydrins, hydroosmotic neurohypophysial peptides: osmoregulatory adaptation in amphibians through vasotocin precursor processing. 278 9

Oxytocin receptors were identified and characterized in bovine mammary tissue. [3H]-oxytocin was specifically bound to the 105,000 X g particulate fractions from 5 lactating cows and 5 non-lactating cows. Binding reached equilibrium by 50 min at 20 degrees C and by 8 hr at 4 degrees C. The half-time of displacement at 20 degrees C was approximately 1 hr. ACTH, TRH, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl- L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive in the dose range tested at 20 degrees C. The ability of other peptides to inhibit 3H-oxytocin binding was as follows: oxytocin greater than vasotocin greater than arginine - vasopressin greater than lysine - vasopressin greater than Pen1 Phe2 Thr4 - oxytocin. The Kd of the oxytocin receptor averaged 1.66 +/- 1.19 nMol/L for lactating cows and 0.97 +/- nMol/L for non-lactating cows, respectively. The maximum number of binding sites was 0.14 +/- 0.12 nM/mg protein and 0.15 +/- 0.08 nM/mg protein for lactating cows and non-lactating cows, respectively. Identification and characterization of these receptors now makes it possible to study the dynamics of hormonal binding throughout various physiological states of the animal.
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PMID:Oxytocin receptors in bovine mammary tissue. 282 Dec 49

An enriched preparation of neurosecretory granules from bovine pituitary neural lobes was used as a source of processing enzymes possibly involved in the cleavage of the proocytocin/neurophysin precursor. A synthetic eicosapeptide reproducing the entire (1-20) sequence of the NH2-terminal domain of the bovine ocytocin/neurophysin precursor was used as a substrate to monitor an endoprotease activity cleaving at the Lys11-Arg12 doublet. The 58-kDa endoprotease detected in the lysate of neurohypophyseal granules produced a single cleavage, after the doublet, at the Arg12-Ala13 peptide bond. This endoprotease with pHi 6.9 and 7.2 exhibits maximal activity at pH around neutrality (7.0) and was strongly inhibited by divalent cation chelating agents [ethylenediaminetetraacetic acid and ethylene glycol bis(beta-aminoethyl ether)-N,N,N',-N'-tetraacetic acid] and to some extent by p-(chloromercuri)benzoate and p-(chloromercuri)benzenesulfonic acid, while phenylmethanesulfonyl fluoride and pepstatin were not active. This endoprotease action was sensitive to any modification of the substrate at either basic amino acid of the doublet since replacement of either L-Lys11 or L-Arg12 by D-Lys or D-Arg and by L-Nle abolished the cleavage reaction. In contrast, reversal of the polarity of the doublet in [Arg11,Lys12]proocytocin/neurophysin(1-20) had no effect on the mode of endoproteolytic cleavage as well as modifications of Gly10 (replaced by Ala10). It is concluded that the selectivity of this endoprotease, which may be involved in the primary event occurring in proocytocin/neurophysin processing, is strictly dependent upon the integrity of the basic doublet but that other parameters determined by the amino acid sequence around this doublet may play an important role.
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PMID:Partial purification and functional properties of an endoprotease from bovine neurosecretory granules cleaving proocytocin/neurophysin peptides at the basic amino acid doublet. 282 69

We examined the effects of oxytocin on renal tubular epithelial LLC-PK1 cells. In cells loaded with Fura 2, we found that 1 microM oxytocin induced a rapid increase in cytosolic free [Ca2+]i from 120 nM to 250 nM within 12 sec. [Ca2+]i then decreased and leveled at 148 nM. Calcium was mobilized from intra- and extra-cellular sources. Oxytocin-induced calcium mobilization was dose dependent (EC50 between 5 and 30 nM). Oxytocin also stimulated calcium efflux which was blocked by the selective oxytocin antagonist KB-5-21. Calcium mobilization was a likely consequence of enhanced phosphatidylinositol turnover, because oxytocin rapidly increased the formation of inositol phosphates including Ins1,4,5P3. Calcium transients were induced by oxytocin and the oxytocin selective analog AM-2-40 and blocked by the oxytocin-selective antagonist KB-5-21. Lysine vasopressin, the selective V2 agonist dDAVP, and the V1-selective agonist SK&F 105349 were at least 10- to 100-fold less potent than oxytocin and exhibited only partial agonist activity. Using peptide analogs, a poor correlation was found between antagonism of oxytocin-induced calcium transients of LLC-PK1 cells and pig kidney V2 and rat liver V1 receptor affinity. These data indicate that oxytocin-induced calcium transients in LLC-PK1 cells were not mediated by V1 or V2 vasopressin receptors, but by oxytocin receptors. However, the poor correlation between antagonism at the LLC-PK1 receptors and the rat uterus oxytocin receptors suggests marked differences in antagonist recognition. We have also identified specific, saturable, high affinity oxytocin-binding sites of low density on intact LLC-PK1 cells (KD = 1.9 nM; Bmax = 3.2 fmol/10(6) cells). The relative analog affinities for these binding sites correlated well with their effects on oxytocin-induced calcium transients. We conclude that in LLC-PK1 cells, oxytocin stimulates a transient rise in cytosolic free [Ca2+]i and the formation of inositol phosphates, including Ins1,4,5P3. The effects on [Ca2+]i probably are not mediated by V1 and V2 vasopressin receptors, but by putative oxytocin receptors.
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PMID:Oxytocin induces a transient increase in cytosolic free [Ca2+] in renal tubular epithelial cells: evidence for oxytocin receptors on LLC-PK1 cells. 282 15

The present study describes the synthesis and biological activities of the photoreactive vasotocin analog 1-deamino[8-lysine(N epsilon-4-azidobenzoyl)] vasotocin ([Mpa1, Lys(N epsilon-4-azidobenzoyl)8]vasotocin). The analog was obtained by introducing the photoreactive aryl azido group at the epsilon-amino group of Lys8 in [Mpa1, Lys8]-vasotocin, which was synthesized by the solid phase method. In the isolated toad urinary bladder the photoaffinity analog of vasotocin retained hydroosmotic activity in the absence of u.v.-light. After irradiation the osmotic water flow across the bladder wall increased. Moreover, the water permeability remained high during repeated periods of washout, suggesting that the analog formed covalent complexes with vasotocin receptors in the toad bladder. In the rat uterotonic assay the photoreactive vasotocin analog was without photoactivation a mild agonist. These studies suggest that the photoaffinity analog of vasotocin might be useful for the isolation of vasotocin receptors in low vertebrates and oxytocin receptors in mammals.
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PMID:Synthesis and biological activities of a photoaffinity probe for vasotocin and oxytocin receptors. 283 Jan 97

Receptors for arginine vasopressin (AVP) were characterized in tubular epithelial basolateral membranes (BL membranes) prepared from the kidneys of male Sprague-Dawley rats. Association of [3H]AVP was rapid, reversible, and specific. Saturation studies revealed a single class of saturable binding sites with a maximal binding (Bmax) of 184 +/- 15 fmol/mg protein and a KD of 0.61 +/- 0.04 nM. IC50S for AVP, lysine vasopressin, and oxytocin were 0.74 nM, 9.7 nM, and greater than 1 microM, respectively. The V2 receptor antagonist was more than 3,700 times as effective in displacing [3H]AVP than was the V1 antagonist. To investigate the physiological regulation of vasopressin receptors, the effects of elevated levels of circulating AVP on receptor characteristics were studied. Seventy-two-hour water deprivation significantly elevated plasma osmolality and caused an 11.5-fold increase in plasma [AVP]. Scatchard analysis revealed a 38% decrease in the number of AVP receptors on the BL membranes from dehydrated animals. The high-affinity binding sites on the BL membranes fit the pharmacological profile for adenylate cyclase-linked vasopressin receptors (V2), which mediate the antidiuretic action of the hormone. We conclude that physiologically elevated levels of AVP can downregulate vasopressin receptors in the kidney.
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PMID:Renal tubular vasopressin receptors downregulated by dehydration. 283 32

The specific binding of [3H]oxytoxin to uterine membrane preparations derived from different species at late pregnancy was examined. The highest receptor density (bmax value) was found in membranes derived from the myometria of guinea pigs between day 60 post-conception (bmax = 3.6 +/- 0.1 pmol/mg) and day 65 (bmax = 4.4 +/- 0.1 pmol/mg). The similarity of Kd values for oxytocin binding (Kd = 2.6 +/- 0.2 nM) and for vasopressin binding (Kd = 2.1 +/- 0.4 nM) to the same membranes derived from a guinea pig myometrium indicate a homogeneous population of high-affinity binding sites which do not discriminate between these two hormones. Competitive binding experiments with specific oxytocin agonists containing either sarcosine or N-methylalanine in the place of Pro7 demonstrated that these myometrial receptors have the pharmacological properties of oxytocin receptors. The analogue of 1-deamino-[8-lysine]vasopressin containing a photoreactive azidophenylamidino group at the sidechain of Lys8 retained roughly the same receptor affinity as oxytocin. In photoaffinity labelling experiments with the tritium-labelled analogue a membrane protein from guinea pig myometrium with an apparent relative molecular mass Mr of 78,000 +/- 5000 (n = 13) was preferentially labelled. The labelling of this protein was completely suppressed by a 100-fold molar excess of either oxytocin, or [Sar7]oxytocin or [Thr4, Sar7]oxytocin, but not by other peptide hormones. These results provide evidence that the labelled 78,000-Mr protein is a myometrial oxytocin-receptor protein.
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PMID:Identification of a myometrial oxytocin-receptor protein. 283 2

In experiments with male white rats it was shown that 0.001 and 0.01 mg/kg of lysyl vasopressin C-terminal fragment--Pro-Lys-Gly (PLG) being injected intraperitoneally fails to influence the acquisition of active and passive avoidance and also T-maze food rewarded behaviour. The injection of PLG removed by disturbances of active avoidance caused by cyproheptadine and oxytocin. The inhibition of passive avoidance and food-rewarded behaviour was not removed by PLG.
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PMID:[The elimination of disorders in the acquisition of a conditioned active avoidance reaction by using the C-termination fragment of lysyl vasopressin]. 284 10


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