Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

N-Methyl-D-Aspartate(NMDA)-sensitive glutamate receptors, are critically involved in the induction of the learning process. Activation of NMDA receptors by glutamate lead to massive influx of extracellular Ca2+, with ensuing activation of a variety of Ca(2+)-dependent enzymes, including protein kinase C. This triggers a cascade of intracellular reactions which is essential for memory formation. In culture neurons, high concentrations of oxytocin (> 1 microM) attenuate the stimulation of 45Ca2+ influx promoted by glutamate through the activation NMDA receptors. In addition, the hormone reduces glutamate-stimulated [3H]4-beta-phorbol 12,13-dibutyrate (PdBu) binding in intact cells, a parameter that reflects the translocation of protein kinase C from the cytosol to the cell membrane. Taken collectively, these results indicate that oxytocin reduces the activity of NMDA receptors, thus impairing one of the major substrates for the induction of learning and memory.
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PMID:Oxytocin reduces the activity of N-methyl-D-aspartate receptors in cultured neurons. 790

Oxytocinergic neurons of the paraventricular nucleus (PVN) of the hypothalamus have been implicated in modulating male sexual responses in rats. Previous investigators have shown that cerebrospinal fluid concentrations of oxytocin (OT) increased after ejaculation and that intraventricular administration of OT and electrolytic lesions of the PVN increased temporal measures of male sexual behavior. Recently, we have demonstrated that OT-immunoreactive neurons in the parvocellular subnuclei of the PVN project to lower levels of spinal cord. In the present study, N-methyl-D-aspartic acid lesions, which have been shown to destroy parvocellular PVN neurons while leaving magnocellular neurons intact, were used to evaluate the role of parvocellular neurons on male copulatory behavior and seminal emissions. OT-immunoreactive fibers were reduced in the lower lumbar spinal cord (L5-L6) following N-methyl-D-aspartic acid lesions in the PVN. This reduction was associated with a significant decrease in seminal emission at the time of ejaculation, but mount, intromission and ejaculatory latencies were unaffected.
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PMID:Effects of paraventricular lesions on sex behavior and seminal emission in male rats. 940 14

A dose of apomorphine or oxytocin that induces penile erection and yawning increases nitric oxide production in the paraventricular nucleus of the hypothalamus, as determined by the increase in NO2- and NO3- concentration induced by these substances in the paraventricular dialysate obtained from male rats. All the above responses were prevented by a dose of omega-conotoxin-GVIA as low as 5 ng. This potent inhibitor of N-type Ca2+ channels was injected into the paraventricular nucleus 15 min before apomorphine (50 ng) or oxytocin (10 ng). In contrast, omega-conotoxin was ineffective when the above responses were induced by N-methyl-D-aspartic acid (50 ng). The peptide toxin (5 ng) was also ineffective on the penile erection and yawning induced by the nitric oxide donors sodium nitroprusside (50 microg) or hydroxylamine (50 microg), injected into the paraventricular nucleus. The present results suggest that omega-conotoxin-sensitive Ca2+ channels are involved in the activation of nitric oxide synthase, penile erection and yawning induced by apomorphine and oxytocin, but not by N-methyl-D-aspartic acid, at the paraventricular level.
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PMID:Different effects of omega-conotoxin on penile erection, yawning and paraventricular nitric oxide in male rats. 983 Dec 88

The aim of this study was to investigate the molecular changes associated with the transition of the human oxytocin receptor from its inactive to its active states. Mutation of the conserved arginine of the glutamate/aspartate-arginine-tyrosine motif located in the second intracellular domain gave rise to the first known constitutively active oxytocin receptor (R137A), whereas mutation of the aspartic acid located in the second transmembrane domain led to an inactive receptor (D85A). The structural features of the constitutively active and inactive receptor mutants were compared with those of the wild type in its free and agonist-bound states. The results suggest that, although differently triggered, the activation process induced by the agonist and the activating mutation are characterized by the opening of a solvent exposed site formed by the 2nd intracellular loop, the cytosolic extension of helix 5, and the 3rd intracellular loop; on the contrary, the D85A mutation prevents oxytocin from triggering the opening of a cytosolic site. On the basis of these findings, we hypothesize that this cytosolic crevice plays an important role in G protein recognition. Finally, comparative analysis of the free- and agonist-bound forms of the wild-type oxytocin receptor and alpha1B adrenergic receptor suggests that the highly conserved polar amino acids and the seven helices play similar mechanistic roles in the different G protein-coupled receptors.
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PMID:Activation mechanism of human oxytocin receptor: a combined study of experimental and computer-simulated mutagenesis. 1038 3

In chickens, oviposition is correlated with increased plasma levels of the neurohypophysial hormone vasotocin, and vasotocin stimulates contraction of uterine strips in vitro. A gene encoding a vasotocin receptor subtype that we have designated the VT1 receptor was cloned from the domestic chicken. The open reading frame encodes a 370-amino acid polypeptide that displays seven segments of hydrophobic amino acids, typical of guanine nucleotide-protein-coupled receptors. Other structural features of the VT1 receptor include two potential N-linked glycosylation sites in the extracellular N-terminal region, a conserved aspartic acid in transmembrane domain 2 that is found in nearly all guanine nucleotide-protein-coupled receptors, and two potential protein kinase C phosphorylation sites in the third intracellular loop and C-terminal tail. Expressed VT1 receptors in COS7 cells bind neurohypophysial hormones with the following rank order of potency: vasotocin congruent with vasopressin > oxytocin congruent with mesotocin > isotocin. In addition, the expressed VT1 receptor mediates vasotocin-induced phosphatidylinositol turnover and Ca(2+) mobilization. In the chicken, expression of VT1 receptor gene transcripts is limited to the shell gland (uterus) and the brain. Thus, the VT1 receptor that we have cloned may mediate contractions of the shell gland during oviposition and activate reproductive behaviors known to be stimulated by vasotocin in lower vertebrates.
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PMID:Molecular cloning and functional characterization of a vasotocin receptor subtype that is expressed in the shell gland and brain of the domestic chicken. 1061 Oct 61

The effect of muscimol and baclofen injected into the paraventricular nucleus of the hypothalamus on penile erection and yawning induced by apomorphine, oxytocin and N-methyl-D-aspartic acid (NMDA) was studied in male rats. Muscimol (20-200 ng), but not baclofen (200 ng), injected into the paraventricular nucleus of the hypothalamus 10 min before apomorphine (50 ng), oxytocin (10 ng) or NMDA (50 ng) reduced penile erection and yawning induced by the above compounds given into the paraventricular nucleus. Bicuculline (250 ng) injected into the paraventricular nucleus 5 min before muscimol (100 ng) prevented the inhibitory effect of muscimol on penile erection and yawning induced by apomorphine, oxytocin and NMDA. The present results show that gamma-aminobutyric acid (GABA) inhibits penile erection and yawning by acting on GABA(A) receptors in the paraventricular nucleus of the hypothalamus.
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PMID:Activation of gamma-aminobutyric acid(A) receptors in the paraventricular nucleus of the hypothalamus reduces apomorphine-, N-methyl-D-aspartic acid- and oxytocin-induced penile erection and yawning in male rats. 1070 59

The effect of hexarelin and four related peptide analogues, EP 40904, EP 40737, EP 50885 and EP 60761, injected into the paraventricular nucleus of the hypothalamus of male rats in doses between 2 and 2000 ng on spontaneous penile erection was studied. Of these peptides, EP 60761 and EP 50885, but not hexarelin, EP 40904 or EP 40737, increased dose-dependently the number of spontaneous penile erections. EP 60761 was active already at the dose of 20 ng, which induced the sexual response in 70% of the treated rats. The maximal response was induced by 200 ng of the peptide. EP 50885 was less potent than EP 60761, with 1000 ng being the minimal effective dose and 2000 ng as the dose required to induce the maximal response. At the doses used, both peptides also increased slightly the number of spontaneous yawning episodes. EP 60761- and EP 50885-induced penile erection was prevented by the oxytocin receptor antagonist [d(CH(2))(5)Tyr(Me)(2)-Orn(8)]vasotocin (0.1-1 microg) given intracerebroventricularly (i.c.v.), but not into the paraventricular nucleus (0.1-1 microg), by the competitive nitric oxide (NO) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) given either into the paraventricular nucleus (10-20 microg) or i.c.v. (75-150 microg), by the N-type Ca(2+) channel blocker omega-conotoxin-GVIA (2-5 ng) or by the opiate morphine (1-10 microg), but not by the dopamine receptor antagonist (Z)-4-[3-[2-(trifluoromethyl)-9H-thioxanthen-9-ylidene]propyl]-1-p ipe razine-ethanol (cis-flupenthixol) (10 microg) or by the N-methyl-D-aspartic acid (NMDA) receptor antagonist (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine ((+)-MK-801) (1 microg), all given into the paraventricular nucleus before either peptide. The present results show that EP 60761 and EP 50885 induced penile erection by increasing central oxytocin transmission, possibly by activating NO synthase in the cell bodies of oxytocinergic neurons located in the paraventricular nucleus that control penile erection.
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PMID:EP 60761 and EP 50885, two hexarelin analogues, induce penile erection in rats. 1098 Feb 72

The present study aimed to examine roles of N-methyl-D-aspartic acid (NMDA) receptors in oxytocin and vasopressin release after osmotic stimuli. A noncompetitive NMDA receptor antagonist, MK-801 (0.2 mg/kg body weight, i.p.), significantly decreased plasma concentrations of oxytocin and vasopressin after hypertonic saline injection (0.3 or 0.6 M NaCl, i.p., 20 ml/kg). By contrast, oxytocin release induced by injection of cholecystokinin octapeptide (20 microg/kg, i.p.) was not significantly changed by MK-801. Hypertonic saline injection increased the number of cells expressing Fos in the supraoptic nucleus and in the regions anterior and ventral to the third ventricle (AV3V) regions [the organum vasculosum of the lamina terminalis (OVLT) and median preoptic nucleus]. MK-801 decreased the number of cells expressing protein in these areas after hypertonic saline injection. A microdialysis method showed that a hypertonic saline injection (0.6 M NaCl, 20 ml/kg, i.p.) facilitated glutamic acid release in and near the OVLT. The results support the view that NMDA receptor in the AV3V region modulates in a facilitative fashion the AV3V inputs to the supraoptic neurosecretory neurones.
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PMID:Involvement of N-methyl-D-aspartic acid receptor activation in oxytocin and vasopressin release after osmotic stimuli in rats. 1116 42

Yawning is a phylogenetically old, stereotyped event that occurs alone or associated with stretching and/or penile erection in humans, in animals from reptiles to birds and mammals, under different conditions. Several neurotransmitters and neuropeptides are involved in its control at the central level. One of these at the level of the paraventricular hypothalamic nucleus (PVHN) is nitric oxide (NO). First, NO synthase inhibitors injected into this hypothalamic nucleus prevent yawning induced by dopamine agonists, oxytocin or N-methyl-D-aspartic acid (NMDA), which induce yawning by activating PVHN oxytocinergic neurons projecting to extra-hypothalamic brain areas. The inhibitory effect of NO synthase inhibitors was not observed when these compounds were given concomitantly with L-arginine, the precursor of NO. Second, dopamine agonists, NMDA and oxytocin given at doses that induce yawning, increase NO production in the PVHN, as determined by in vivo microdialysis. Conversely, the opiate morphine, which prevents yawning induced by dopamine agonists, oxytocin and NMDA, also prevents the increase in the paraventricular NO production induced by these compounds. Third, NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylamine, induce yawning when injected into the PVHN apparently by activating oxytocinergic transmission. Since guanylate cyclase inhibitors and NO scavengers (hemoglobin) injected into the PVHN do not prevent drug-induced yawning, nor 8-Br-cGMP injected into the PVHN induces this behavioral response, it is likely that NO acts as an intracellular rather than an intercellular modulator inside the PVHN oxytocinergic neurons in which NO is formed to facilitate the expression of this phylogenetically old event by guanylate cyclase-independent mechanisms.
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PMID:Yawning: role of hypothalamic paraventricular nitric oxide. 1124 84

The effect of 10 peptides structurally related to the growth hormone (GH) releasing peptide hexarelin, injected into the paraventricular nucleus of the hypothalamus (PVN), on penile erection was studied in male rats. Six out of the 10 peptides tested induced penile erection in a dose-dependent manner. Among them, the most potent were EP 80661, EP 60761 and EP 91072, which were active at doses of 20-200 ng. The potency of these peptides in inducing penile erection is comparable to that of apomorphine, oxytocin and N-methyl-D-aspartic acid similarly injected into the PVN. Other peptides found active were EP 50885, EP 90101 and EP 91071, which induced penile erection at doses of 200-2000 ng. In contrast, EP 51322, EP 70555, EP 51216 and EP 91073 were inactive, as were hexarelin, EP 40904 and EP 40737 in a previous study. The majority of EP peptides found active when injected into the PVN induced penile erection, although to a lesser extent, also when given systemically (endovenously). The proerectile effect of EP peptides was prevented by the oxytocin receptor antagonist [d(CH2)5 Tyr(Me)2-Orn8]-vasotocin given into the lateral ventricles but not into the PVN, by the nitric oxide (NO) synthase inhibitor N(G)-nitro-1-arginine methyl ester given either into the lateral ventricles or into the PVN, by the N-type Ca2+ channel blocker omega-conotoxin GVIA and by morphine, but not by the dopamine receptor antagonist cis-flupenthixol or by the N-methyl-D-aspartic acid receptor antagonist dizolcipine, given into the PVN. As the structure-activity relationship of EP peptides for proerectile activity is different from those of other biological actions of these compounds, ie for GH release and eating behaviour, the present results suggest that EP peptides induce penile erection by acting on specific hypothalamic receptor sites that activate paraventricular oxytocinergic neurons projecting to extrahypothalamic brain areas that mediate this sexual function by a mechanism similar to that of dopamine receptor agonists, oxytocin and N-methyl-D-aspartic acid.
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PMID:EP 60761- and EP 50885-induced penile erection: structure-activity studies and comparison with apomorphine, oxytocin and N-methyl-D-aspartic acid. 1142 62


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