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 different doses of lysine vasopressin (LVP) and oxytocin (OXT) were studied on the six-day acquisition or extinction of a food-reinforced classical conditioning reflex (conditional stimulus: light) when intraperitoneal (ip.) injections were carried out 20 min prior to the behavioural sessions. The highest (600 mU/kg) dose of LVP inhibited acquisition, and all LVP doses tested (150, 300 and 600 mU/kg) facilitated the extinction of conditioned behaviour. These same mU doses of OXT did not significantly affect the food-reinforced conditioning, although a consequent tendency towards increased performance (the opposite action to vasopressin) was observed. When 2.5 or 25 micrograms/kg doses of desglycinamide-arginine-vasopressin (DGAVP), a 500 micrograms/kg dose of prolyl-leucyl-glycinamide (PLG) or a 1200 mU/kg dose of OXT was injected during the extinction sessions, 2.5 micrograms/kg DGAVP and 1200 mU/kg OXT significantly facilitated extinction; the other treatments were without effect. LVP in a dose of 300 or 600 mU/kg and OXT in a dose of 300, 600 or 1200 mU/kg did not influence the food intake of 22 h food-deprived rats in a nonconditional situation. The present results indicate that the effects of LVP and OXT on memory display reinforcement-dependent characteristics, and are thus indirect or non-specific in nature.
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PMID:Effects of neurohypophyseal hormones on food-reinforced classical conditioning in the rat. 289 68

Two neuropeptide precursor processing enzyme systems were characterized in the rat brain cortex and bovine neurohypophysis and corpus luteum. The first one combines the action of a 90 kDa endoprotease which cleaves somatostatin-28 before the Arg-Lys doublet and that of an aminopeptidase B-like enzyme. The second system associates the action of a 58 kDa endoprotease cleaving pro-ocytocin/neurophysin (1-20) after the Lys-Arg dibasic moiety and a carboxypeptidase B-like activity. Both systems appear to be located in membrane-limited secretory vesicles of the producing organs, and to exhibit the properties of metallo-enzymes sensitive to divalent cation chelators. In contrast, they do not show the characteristics of serine-proteases and of trypsin-like enzymes. Studies with substrate analogs selectively modified at the basic doublet indicated that the integrity of both basic amino acids is essential but that conformational parameters, probably governed by the amino acid sequences flanking the basic doublet, play an important role. These data will be discussed in relation to a hypothesis on the predicted preferred secondary structure of these restriction loci.
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PMID:Somatostatin-28 and pro-ocytocin/neurophysin convertases: basic pair selective endoproteases involved in pro-hormone processing in the rat brain cortex and bovine corpus luteum. 290 27

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

[3H]1-Desamino-8-D-arginine vasopressin [3H] DDAVP was assessed as a radioligand for vasopressin V2-receptors by studying its membrane-binding characteristics and in vitro autoradiographic localization in rat kidney, a rich source of V2-receptors. [3H]DDAVP bound specifically to a single class of high affinity, low capacity sites in rat medullopapillary membranes. Specific [3H]DDAVP binding at 25 C reached equilibrium after 2 h of incubation and was saturable and linear with protein concentration up to 2.2 mg/ml protein. Saturation analysis gave an equilibrium dissociation constant (Kd) of 0.76 nM. Displacement of [3H]DDAVP binding by unlabeled arginine vasopressin (AVP) and related analogs gave the following order of potency, consistent with that expected for a V2-receptor: DDAVP approximately equal to AVP approximately equal to 1-desamino-AVP greater than lysine vasopressin greater than oxytocin greater than [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid, 2-(O-methyl)tyrosine]AVP. The C-terminal metabolites of AVP, (pGlu4Cyt6)AVP-(4-9), and (pGlu4Cyt6)AVP-(4-8) did not displace [3H]DDAVP binding. No degradation of [3H] DDAVP during incubation could be detected by HPLC analysis. In vitro autoradiography of [3H]DDAVP binding to rat kidney sections showed a very dense localization of displaceable binding over inner and outer medulla, with a much lower density in cortex, consistent with the known major localization of V2-receptors on renal collecting tubules. These studies suggest that [3H]DDAVP is a suitable radioligand for labeling V2-receptors and may be useful in the characterization of vasopressin receptor subtypes in a variety of tissues and in purification of the V2-receptor.
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PMID:Properties of [3H]1-desamino-8-D-arginine vasopressin as a radioligand for vasopressin V2-receptors in rat kidney. 296 62

The exposure of WRK1 cells to arginine vasopressin (AVP), lysine vasopressin, or oxytocin for 18 h at 37 degrees C induced a homologous desensitization of the vasopressin- (VP) receptors. Dose-response curves of [3H]lysine vasopressin binding to control and desensitized WRK1 cells revealed a decrease in the maximal number of binding sites without any modification of its affinity (Kd values = 4.40 +/- 0.76 nM and 4.65 +/- 0.78 nM for control and desensitized conditions, respectively). The phenomenon was time- and dose-dependent. It was directly related to receptor occupancy, since the concentration of VP analogues leading to a half-maximal occupancy of VP receptors was closely related to the concentration of the corresponding analogue leading to a half-maximal decrease in VP-binding sites. It was also agonist-specific, since the V1 vasopressin antagonist desGly9d(CH2)5[D-Tyr(Et)2]VAVP was unable to affect the number of receptors. These desensitization processes were completely inhibited when the functional coated pits present in WRK1 cells were suppressed, indicating that the loss of VP-binding sites was related to receptor internalization. The exposure of WRK1 cells to a vasopressin agonist for 18 h also led to an inhibition of the vasopressin-sensitive phospholipase C activity. It was time- and agonist-dose-dependent, and occurred without any detectable changes in apparent affinity values (1.40 +/- 0.04 and 1.90 +/- 0.36 nM for control and desensitized cells, respectively). Control experiments showed that these inhibitions could not have been caused by a decrease in the labeling of inositol lipids. It is likely that they were mainly due to receptor internalization since (i) the hormonal treatment did not modify the basal level of phospholipase C; (ii) the maximal loss of VP-binding site was similar to the maximal inhibition of VP-stimulated IP accumulation; (iii) the recoveries of both VP-binding sites and VP-sensitive phospholipase C activity followed exactly the same time course (t1/2 = 4 h). In addition to this homologous desensitization of VP-sensitive phospholipase C activity, AVP also induced heterologous desensitization of bradykinin-sensitive phospholipase C activity. However, this effect was relatively weak (maximal inhibition 17 +/- 3%). The time course of VP-sensitive phospholipase C desensitization was more rapid than that of VP-receptors, indicating that desensitization involved at least two distinct steps, a rapid uncoupling step, and a later loss of vasopressin receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence of two steps in the homologous desensitization of vasopressin-sensitive phospholipase C in WRK1 cells. Uncoupling and loss of vasopressin receptors. 296 82

Immunoreactive AVP was found to be much higher in platelets than in platelet-free plasma (PFP) in normal subjects (12.8 +/- 6.3 versus 1.7 +/- 0.8 fmol/ml). AVP levels in PFP were appreciably elevated in parallel with the elevation of plasma osmolality induced by the acute osmotic stimulation, while the AVP levels in platelets did not change before and after the stimulation. Binding studies on intact platelets demonstrated specific binding sites for [3H]AVP. The specific binding was time, temperature and concentration-dependent, saturable and reversible, with the maximal binding capacity (Bmax) of 169.9 +/- 14.4 sites/platelet and affinity of 4.84 +/- 1.15 x 10(8)M-1. The affinity constants for unlabelled AVP, lysine vasopressin (LVP), oxytocin (OT) and dDAVP were 9.0, 8.5, 7.4 and 6.6, respectively, and the inhibition constant for d(CH2)5Tyr(Me)AVP (V1-antagonist) was 7.7. There was a highly significant correlation between the affinity constants of AVP analogues and their relative vasopressor activities in vivo, whereas no such correlation was found between the affinity constants and antidiuretic activities. AVP caused platelet aggregation with the maximal aggregation of 48.0 +/- 25.1% at 230 nM of AVP. A significant correlation was observed between the maximal percentage aggregation and Bmax of [3H]AVP to intact platelets. These results suggest that the platelet vasopressin receptor belongs to the V1 vascular subtype and mediates platelet aggregation.
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PMID:Characterization of human platelet vasopressin receptor and the relation between vasopressin-induced platelet aggregation and vasopressin binding to platelets. 297 18

We have previously shown that arginine vasopressin (AVP) directly inhibits testicular steroidogenesis in vitro. In the present study, binding of neurohypophysial peptides to interstitial cells of the rat testis was studied using [3H]AVP as the ligand. Interstitial cells were obtained from adult rat testis after collagenase dispersion and were incubated with [3H]AVP in the presence or absence of unlabeled AVP. Binding equilibrium was reached by 60 min at 4 C, while incubation at higher temperatures (23 and 37 C) resulted in an apparent decrease in binding. Scatchard plot analysis of equilibrium binding data revealed the existence of one class of high affinity, low capacity binding sites (Kd = 1.0 +/- 0.3 nM; maximal binding = 8.5 fmol/10(6) cells). In addition, the rate constants of association and dissociation were calculated to be 0.024 nM-1 min-1 and 0.009 min-1, respectively. Addition of naturally occurring neurohypophysial hormones as well as their synthetic analogs inhibited [3H]AVP binding to testis cells, resulting in parallel displacement curves. The order of potencies for the native peptides was: AVP = lysine vasopressin = arginine vasotocin (IC50, 5 X 10(-10) M) greater than oxytocin = mesotocin (IC50, 4 X 10(-7) M) greater than isotocin = glumitocin (IC50 greater than 10(-6) M). Furthermore, two potent vasopressor antagonists, d(CH2)5Tyr(Me)AVP ([1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]AVP) and dPTyr(Me)AVP ([1-deaminopenicillamine-2-(O-methyl)tyrosine]AVP) competed for [3H]AVP binding with a higher affinity (IC50, approximately 10(-11) M) than native AVP. In contrast, a selective antidiuretic agonist, dDAVP (1-deamino-8-D-AVP), only competed weakly for receptor binding, while a specific oxytocic agonist, (Thr4,Gly7)oxytocin, did not affect AVP binding. These results suggested that the testis may contain the V1 receptor subtype. Studies on the intratesticular distribution of AVP receptors indicated minimal binding to cells derived from the seminiferous tubule, while most of the AVP-binding sites sediment with enriched fractions of Leydig cells after Metrizamide density gradient centrifugation. AVP-binding sites were also found in rat liver, kidney, and anterior pituitary (10.7, 2.6, and 1.7 fmol/mg protein), whereas adrenal, cerebellum, prostate, and hypothalamus were devoid of AVP-binding sites. Thus, we have demonstrated the presence of high affinity, stereospecific receptors for AVP in the interstitial cell compartment of the rat testis. These V1 receptors may mediate the direct inhibitory action of neurohypophysial hormones on testicular Leydig cell steroidogenesis.
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PMID:Identification and characterization of arginine vasopressin receptors in the rat testis. 298 Oct 73

Specificity of binding of 3H-labeled arginine vasopressin [( 3H]AVP), down-regulation of receptors, and desensitization were studied in anterior pituitary glands of both Wistar and Brattleboro rats. Studies using both crude membrane fractions and isolated cells of anterior pituitaries revealed the presence of a single population of binding sites with a Kd of approximately 1 nM. The receptor recognized the following peptides, with AVP = lysine vasopressin = vasotocin greater than oxytocin = 1-deamino-(8-D-AVP) greater than d-(CH2)5-Tyr-(Me)-Val4-AVP greater than 1-deaminopenicillamine-(Val4-D-Arg8)VP. Neither corticotropin-releasing factor (CRF) nor any of the neuropeptides tested, including AVP ring and tail fragments, competed for tracer binding. Increased extracellular vasopressin levels due to chronic injections or long term adrenalectomy decreased receptor density by 80%, while oxytocin was less effective than AVP. Comparing binding data in Brattleboro homozygotes and heterozygotes revealed that AVP levels within the physiological range could down-regulate pituitary receptors as well. This could not be caused by occupation of sites by endogeneous vasopressin, since injection of large doses of peptide decreased tracer binding by less than 10%. Loss of pituitary receptors reduced 1) enhancement by AVP of CRF-induced cAMP accumulation, 2) intrinsic CRF-like activity and 3) synergistic effect of AVP on ACTH secretion elicited by CRF. This study thus provides evidence for the presence of highly specific vasopressin receptors in the anterior pituitary, which may undergo homologous down-regulation and desensitization in terms of cAMP production and ACTH release.
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PMID:Specific receptors for vasopressin in the pituitary gland: evidence for down-regulation and desensitization to adrenocorticotropin-releasing factors. 298 73

Biological and immunological relationships between molt-inhibiting hormone (MIH) activity in eyestalk ganglia extracts of the crab, Cancer antennarius Stimpson, and peptides of the vasopressin-oxytocin family were assessed. Lysine vasopressin (LVP), arginine vasopressin (AVP), vasotocin (VT), and oxytocin (OT) mimicked MIH action by inhibiting ecdysteroid production of Y-organ segments in vitro with the relative potencies LVP greater than AVP greater than VT much much greater than OT. The inhibitory effect was reversible and specific (6 other peptides did not alter Y-organ activity). MIH and LVP increased Y-organ cyclic adenosine 3',5' monophosphate (cAMP) levels dose-dependently and with identical time course in which the rise in cAMP preceded inhibition of ecdysteroid production. The synthetic vasopressin antidiuretic agonist 1-deamino-8-D-AVP (dDAVP) inhibited Y-organ steroidogenesis dose-dependently; the vasopressin analog ([1(B-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine[AVP) (d(CH2)5Tyr(Me)AVP), a vasopressor antagonist, had no effect on basal or MIH-suppressed steroidogenesis. AVP antiserum abolished the inhibitory action of MIH, LVP, and AVP. Competitive binding curves for MIH, LVP, AVP, VT, and OT with the AVP antiserum suggested that MIH is most closely related to LVP. MIH may be structurally related to the vasopressins and act on Y-organ cells via type V2 (cAMP-linked) receptors.
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PMID:Functional relations of crab molt-inhibiting hormone and neurohypophysial peptides. 299 30

We have previously demonstrated that intracerebroventricular (ICV) administration of oxytocin (OXY) enhanced grooming behaviors in male and female rats at a 1 microgram dose. In the present study female rats were injected ICV with 1 microgram OXY or equimolar doses of other peptides. At this dose arginine-vasopressin (AVP), arginine-vasotocin (AVT) and lysine-vasopressin (LVP), as well as alpha-MSH, were as effective as OXY in increasing grooming behavior. At equimolar doses, ACTH1-10, tocinoic acid (the ring structure of OXY) and Pro-Leu-Gly-NH2 (the tail structure of OXY) had no significant effect on grooming behavior. The potency of AVP and AVT was determined across a 0.05-5 microgram dose range. Grooming scores increased in an apparent linear manner across a similar OXY dose range. Both AVP and AVT, however, manifested an inverted U grooming response curve. Maximum grooming scores resulted from a 0.1 microgram dose of AVT or a 0.5 microgram AVP dose. Analyses of the aspects of grooming separately found that nonapeptides OXY, AVP and AVT all elevated body grooming, washing, and scratching. Because AVT and AVP administration resulted in grooming scores significantly higher than OXY at lower doses, we concluded that the CNS is more sensitive to the effects of AVT and AVP on grooming behavior than OXY.
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PMID:A comparison of grooming behavior potencies of neurohypophyseal nonapeptides. 301 15


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