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)

The role of the oxytocin-containing projections to the autonomic nuclei of the spinal cord for lower urinary tract function has not been clarified. The hypothesis was tested that oxytocin acts as a mediator of bladder contraction at the spinal cord level. In conscious female rats undergoing continuous cystometry, intrathecal oxytocin (30 ng approximately 30 pmoles) significantly increased micturition pressure (P<0.001), and decreased bladder capacity (P<0.01) and micturition volume (P<0.01). Residual volume increased (P<0.05), and so did the amplitude and frequency of non-voiding contractions (P<0.01). Immediately after administration of oxytocin, the animals showed frequent stretching movements and yawning, and they licked their tails. The effects of oxytocin were dose-dependent; high concentrations (100 ng) were ineffective. Intra-arterial injection of oxytocin (30 ng) near the bladder had no effect. In isolated detrusor strips, oxytocin caused a concentration-dependent contraction; the concentration response curve was concentration-dependently shifted to the right by the oxytocin antagonist, 1-deamino, 2-D-Tyr(OEt), 4-Thr, 8-Orn-OT. Intrathecal injection of the antagonist (500 ng), had per se no effect on micturition. However, when the antagonist was given intrathecally 4-5 min prior to intrathecal oxytocin (30 ng), the effects of oxytocin were reduced or completely prevented. When given after intrathecal administration of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, intrathecal oxytocin (30 ng) abolished micturition within 5-7 min; all animals developed overflow incontinence, and paralysis of the hindlimbs. These results suggests that in the rat, oxytocin, released from descending pathways, may act as a modulator of the micturition reflex at the spinal level, and that it may interact with nitric oxide. The physiological implications of the findings remain to be established.
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PMID:Oxytocin-induced stimulation and inhibition of bladder activity in normal, conscious rats--influence of nitric oxide synthase inhibition. 968 50

Using the immunohistochemical localization of the protein product of the immediate early gene, c-fos, to localize activated neurons in the paraventricular nucleus of the hypothalamus (PVN), we studied the chemical phenotypes of neurons activated by circulating angiotensin II (AII). We determined the proportions of activated PVN neurons that expressed AII type I receptor-like immunoreactivity (AT1-L) or the neurohormones vasopressin (VP) and oxytocin (OXY). In addition, we identified activated PVN neurons that putatively produce nitric oxide (NO) on the basis of histochemical staining for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). Conscious rats received intravenous AII infusions at a rate sufficient to elevate mean arterial pressure by 40-60 mmHg for 90 min; control rats received infusions of vehicle. Brains were prepared for double immunohistochemistry [Fos-like immunoreactivity (FLI)/AT1-L, FLI/VP or FLI/OXY] or FLI/ NADPH-d histochemistry. Systemic AII infusions led to activation of 149+/-14 PVN neurons per section. In contrast, control animals showed activation of 21+/-6 PVN neurons per section. AII infusions elicited the activation of the following numbers of chemically identified PVN neurons per section: AT1-L, 24+/-5; VP, 26+/-5; OXY, 11+/-2; NADPH-d, 22+/-4. Control animals had few activated PVN neurons per section. For each of the chemically identified populations of PVN neurons, the following proportions were activated: AT1-L, 12.5%; VP, 15.2%; OXY, 7.2%; NADPH-d, 17.3%. The results suggest that PVN neurons producing the AT1 receptor, VP, OXY, and NO, participate in the mediation of the central responses to circulating AII.
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PMID:Activation by systemic angiotensin II of neurochemically identified neurons in rat hypothalamic paraventricular nucleus. 968 48

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 gas nitric oxide (NO) is an important messenger in brain signaling. Along with many other functions, NO is thought to influence the expression and/or release of various hypothalamic hormones (corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH) and vasopressin). To learn more about the role of NO in neuroendocrine mechanisms, we studied in mutant mice lacking neuronal isoform of NO synthase (nNOS) the cellular expression of CRH, neurophysin (the carrier protein of vasopressin/oxytocin) and pro-opiomelanocortin (POMC), as well as of the POMC-derived peptides beta-endorphin (beta-END), alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin (ACTH) by use of immunohistochemistry and in situ hybridization. Additionally, the remaining NO-generating capacities of the nNOS minus mice were investigated by NADPH-diaphorase histochemistry and citrulline immunohistochemistry as well as by immunohistochemical localization and Western blot analysis of endothelial NOS (eNOS) and nNOS isoforms. Amongst all hypothalamic peptides under investigation, only beta-END was found to be altered in mutant mice. A morphometric analysis of beta-END producing neurons of the arcuate nucleus revealed that significantly less cells were immunoreactive in mutant mice, whereas the expression of the precursor POMC as well as of other POMC-derived peptides was found to be unchanged. In addition to that, fewer beta-END-immunoreactive fibers were found in the paraventricular nucleus of nNOS minus mice in comparison to wild-type animals. Hence, the reduction of hypothalamic beta-END is probably a posttranslational event that might reflect a disturbed endorphinergic innervation of those hypothalamic neurons which normally express nNOS.
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PMID:Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase: reduced beta-END immunoreactivity in the arcuate nucleus. 987 4

This brief review emphasizes the importance of three novel discovered factors produced by fetal membranes, placenta and/or by the fetus itself in regulating uterine contractility. We have shown that, as reported for other hormones and substances, nitric oxide and endothelin may influence myometrial activity in an autocrine/paracrine manner interacting with other well-known agents such as prostaglandins, oxytocin and hormones. We also demonstrated that different isoforms of nitric oxide synthase (NOS) may play different roles throughout gestation and during labor. We have suggested that another peptide produced by trophoblast cells, adrenomedullin, may affect, directly or indirectly, myometrial contractility during pregnancy, although much remains to be learned about the mechanisms controlling adrenomedullin expression by the feto-placental tissues cells during pregnancy. Continued research is necessary to better define the complex interactions that result in parturition, both at term and preterm, and to allow a more rational approach to management of the premature labor, exploring new possible pharmacological solutions.
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PMID:New peptides, hormones and parturition. 1006 69

Pharmacological studies in humans and animals suggest the existence of vascular endothelial vasopressin (AVP)/oxytocin (OT) receptors that mediate a vasodilatory effect. However, the nature of the receptor subtype(s) involved in this vasodilatory response remains controversial, and its coupled intracellular pathways are unknown. Thus, we set out to determine the type and signaling pathways of the AVP/OT receptor(s) expressed in human vascular endothelial cells (ECs). Saturation binding experiments with purified membranes of primary cultures of ECs from human umbilical vein (HUVEC), aorta (HAEC), and pulmonary artery (HPAEC) and [3H]AVP or [3H]OT revealed the existence of specific binding sites with a greater affinity for OT than AVP (Kd = 1.75 vs. 16.58 nM). Competition binding experiments in intact HUVECs (ECV304 cell line) with the AVP antagonist [125I]4-hydroxyphenacetyl-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-NH2 or the OT antagonist [125I]D(CH2)5[O-Me-Tyr-Thr-Orn-Tyr-NH2]vasotocin, and various AVP/OT analogs confirmed the existence of a single class of surface receptors of the classical OT subtype. RT-PCR experiments with total RNA extracted from HUVEC, HAEC, and HPAEC and specific primers for the human V1 vascular, V2 renal, V3 pituitary, and OT receptors amplified the OT receptor sequence only. No new receptor subtype could be amplified when using degenerate primers. DNA sequencing of the coding region of the human EC OT receptor revealed a nucleotide sequence 100% homologous to that of the uterine OT receptor reported previously. Stimulation of ECs by OT produced mobilization of intracellular calcium and the release of nitric oxide that was prevented by chelation of extra- and intracellular calcium. No stimulation of cAMP or PG production was noted. Finally, OT stimulation of ECs led to a calcium- and protein kinase C-dependent cellular proliferation response. Thus, human vascular ECs express OT receptors that are structurally identical to the uterine and mammary OT receptors. These endothelial OT receptors produce a calcium-dependent vasodilatory response via stimulation of the nitric oxide pathway and have a trophic action.
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PMID:Human vascular endothelial cells express oxytocin receptors. 1006 57

The present study examined how arginine vasopressin (AVP) affects nitric oxide (NO) metabolism in cultured rat glomerular mesangial cells (GMC). GMC were incubated with test agents and nitrite, and intracellular cGMP content, inducible nitric oxide synthase (iNOS) mRNA, and iNOS protein were analyzed by the Griess method, enzyme immunoassay, and Northern and Western blotting, respectively. AVP inhibited lipopolysaccharide (LPS)- and interleukin-1beta (IL-1beta)-induced nitrite production in a dose- and time-dependent manner, with concomitant changes in cGMP content, iNOS mRNA, and iNOS protein. This inhibition by AVP was reversed by V1- but not by oxytocin-receptor antagonist. Inhibition by AVP was also reproduced on LPS and interferon-gamma (IFN-gamma). Protein kinase C (PKC) inhibitors reversed AVP inhibition, whereas PKC activator inhibited nitrite production. Although dexamethasone and pyrrolidinedithiocarbamate (PDTC), inhibitors of nuclear factor-kappaB, inhibited nitrite production, further inhibition by AVP was not observed. AVP did not show further inhibition of nitrite production with actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis. In conclusion, AVP inhibits LPS- and IL-1beta-induced NO production through a V1 receptor. The inhibitory action of AVP involves both the activation of PKC and the transcription of iNOS mRNA in cultured rat GMC.
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PMID:AVP inhibits LPS- and IL-1beta-stimulated NO and cGMP via V1 receptor in cultured rat mesangial cells. 1007 Jan 67

Nitric oxide (NO) synthase (NOS) is active in the gravid uterus, and its activity decreases prior to the onset of parturition. We tested the hypothesis that NO helps maintain uterine quiescence by suppressing the expression of genes necessary for parturition. Pregnant rats (18 days gestation) were treated with inducible NOS (iNOS) inhibitor N-iminoethyl-L-lysine (NIL) or endothelial NOS inhibitor nitro-L-arginine methyl ester (L-NAME); 24 h later, uteri were analyzed for myometrial connexin 43 (Cx43) protein by immunoblotting and mRNA by Northern analysis. Myometrial oxytocin receptors (OTR) were measured by radioligand binding, and decidual prostaglandin H synthase (PGHS) protein by immunoblotting. Uterine NOS blockade was verified by NOS activity assay. We found that NIL, but not L-NAME, significantly increased myometrial Cx43 protein to parturitional levels with treatment at 19 but not 17 days gestation. Steady state mRNA concentrations were not changed at 24 h. NOS inhibition did not increase the concentrations of OTR, or PGHS protein, nor did it decrease maternal serum progesterone. We conclude that endogenous uterine NO from iNOS suppresses myometrial Cx43 gap junction protein expression during rat pregnancy. Although the exact mechanism is unknown, an increase of uterine wall stretch due to inhibition of relaxation could account for increased Cx43 gene transcription.
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PMID:Endogenous nitric oxide suppresses rat myometrial connexin 43 gap junction protein expression during pregnancy. 1037 25

Tumor necrosis factor alpha (TNFalpha) has been shown to be a potent stimulator of prostaglandin (PG) F(2alpha) secretion in the bovine endometrium. The aims of the present study were to determine the cell types in the endometrium (epithelial or stromal cells) responsible for the secretion of PGF(2alpha) in response to TNFalpha, and the intracellular mechanisms of TNFalpha action. Cultured bovine epithelial and stromal cells were exposed to TNFalpha (0.006-6 nM) or oxytocin (100 nM) for 4 h. TNFalpha resulted in a dose-dependent increase of PGF(2alpha) production in the stromal cells (P < 0.001) but not in the epithelial cells. On the other hand, oxytocin stimulated PGF(2alpha) output in the epithelial cells but not in the stromal cells. When the stromal cells were incubated for 24 h with TNFalpha and inhibitors of phospholipase (PL) C or PLA(2), only PLA(2) inhibitor completely stopped the actions of TNFalpha (P < 0.001). When the stromal cells were exposed to TNFalpha and arachidonic acid, the action of TNFalpha was augmented (P < 0.001). When the stromal cells were incubated for 24 h with a nitric oxide (NO) donor (S-NAP), S-NAP stimulated the PGF(2alpha) production dose-dependently. Although an NO synthase (NOS) inhibitor (L-NAME) reduced TNFalpha-stimulated PGF(2alpha) production, an inhibitor of phosphodiesterase augmented the actions of TNFalpha and S-NAP (P < 0. 05). The overall results indicate that the target of TNFalpha for stimulation of PGF(2alpha) production in cattle is the endometrial stromal cells, and that the actions of TNFalpha are mediated via the activation of PLA(2) and arachidonic acid conversion. Moreover, TNFalpha may exert a stimulatory effect on PGF(2alpha) production via the induction of NOS and the subsequent NO-cGMP formation.
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PMID:Production of prostaglandin f(2alpha) by cultured bovine endometrial cells in response to tumor necrosis factor alpha: cell type specificity and intracellular mechanisms. 1077 56

To test the role of nitric oxide (NO) in secretory functions of bovine corpora lutea (CL), two groups of four Holstein heifers each were treated as follows: Group 1, Nomega-Nitro-L-Arginine Methyl Ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on Day 11 or 12 of the cycle and Group 2, L-NAME on Days 17 and 18 of the cycle. All treatments were administered by an intraluteal microdialysis system (MDS). Drugs were infused for 4-hr periods on the designated days, and the treatment periods were preceded and followed by 4-hr control periods. Perfusate and jugular blood samples were collected at half-hour intervals. Perfusate samples were analyzed for progesterone (P4), oxytocin (OT), prostaglandin F2alpha (PGF2alpha), and leukotriene C4 (LTC4); jugular plasma samples were analyzed for P4, OT, and LH. Perfusion of L-NAME on Day 11 or 12 consistently increased P4 concentration in the perfusate, but had no effect on the life span of the CL. Perfusion of L-NAME on Days 17-18 also elevated P4 levels in the perfusate, and in addition, maintained P4 levels in the plasma of three of the four treated animals through Day 25 of the cycle. L-NAME perfusion also increased OT release concomitant with P4 into the perfusate at both the mid- and late-luteal phase treatments. For the most part, concentrations of LH, OT, and P4 in the jugular plasma samples collected during the perfusions were unaffected by treatments. L-NAME perfusion caused small, but significant (P < 0.05) increases in perfusate PGF2alpha and LTC4 at Days 17 and 18 and in LTC4 on Day 11 or 12. These data indicate that NO plays a direct luteolytic role in regression of the bovine CL.
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PMID:Intraluteal administration of a nitric oxide synthase blocker stimulates progesterone and oxytocin secretion and prolongs the life span of the bovine corpus luteum. 1078 47


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