Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Thirty-three amino acids were applied separately in concentrations of 2 to 10 mM to guinea-pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions.2 Glycine and the straight-chain L-alpha-amino acids up to norleucine were active (longer ones not tested); D-isomers were less potent or inactive in these concentrations. The omega-amino acids gamma-aminobutyric acid (GABA) and delta-aminovaleric, and the alpha,omega-diamino acids L-alpha,beta-diaminopropionic and L-alpha,gamma-diaminobutyric were active, whereas others of similar chain-length such as beta-alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido-amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity.3 The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5-hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful.4 When some of the acids that were spasmogenic at 2 to 10 mM were applied at sub-spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations.5 There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.
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PMID:Spasmogenic and potentiating actions of some amino acids on the guinea-pig myometrium. 92 51

A bland procedure, conducted in ice, is described for the extraction with HCl of smooth-muscle-contracting substances from plexus-containing ileal longitudinal muscle (l.m.) sheets obtained mainly from rabbits and some guinea-pigs. The spasmogenic activity in rabbit extracts was distinguished from acetylcholine, histamine and 5-hydroxytryptamine by antagonists; and from prostaglandins, by its insolubility in ether at acid pH and by pretreatment of the animals with indomethacin. The fact that it contracts the separated l.m. of the guinea-pig ileum, whether plexus-containing or plexus-free, and in atropine distinguishes it also from methionine-enkephalin, somatostatin, 13-norleucine motilin, bombesin, and cholecystokinin octapeptide (CCK8). This activity was partially purified, first by several partitions with ether at pH 1.4-2.2 and then by treatment at pH 4.5-5 with lead acetate. The virtual absence of ATP was confirmed by the firefly bioluminescence technique. The guinea-pig-ileum-contracting component in the partially purified extracts was destroyed by pepsin, chymotrypsin and DPCC-treated trypsin, indicating its peptide nature and distinguishing it from oxytocin, vasopressin, bradykinin, etc. In parallel assays the partially purified rabbit extracts were considerably more active than Substance P on jird or rat ascending colons than on the guinea-pig l.m., suggesting the presence of a second spasmogenic component in the extracts. In guinea-pig extracts the partially purified activity was 8-16 times greater when plexus-containing than when plexus-free, pointing to Auerbach's plexus as the source of the activity.
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PMID:Extraction and partial purification of spasmogenic substances in Auerbach's plexus. 242 21

The effects of bPTH-(1-34), oxidized bPTH-(1-34),[Nle8,Nle18, Tyr34] bPTH-(1-34) amide, and oxidized [Nle8,Nle18,Tyr34]bPTH-(1-34)amide were tested in an in vitro rat uterine assay. When bPTH-(1-34) was treated with hydrogen peroxide (H2O2), the ability of this peptide to reduce oxytocin-stimulated uterine contraction in vitro was no longer evident. An analogue of bPTH-(1-34), in which the methionines at positions 8 and 18 were replaced with norleucine ([Nle8,Nle18,Tyr34]bPTH-(1-34)amide), was capable of reducing oxytocin-stimulated uterine contraction. However, when the [Nle8,Nle18,Tyr34]bPTH-(1-34)amide was oxidized, it retained the ability to reduce uterine contraction. Since we have previously shown that H2O2 oxidation affected only the methionines, these results suggest that the methionines are not necessary for the uterine activity of bPTH-(1-34). We have previously shown that oxidation of bPTH-(1-34) also destroys its blood vessel relaxing activity but has no effect in the rat or the Japanese quail hypercalcemic assays. These data combined with the results of the present studies suggest that the uterine and vascular smooth muscle relaxing properties of bPTH-(1-34) may require the same structural conformation and that this conformation is different from that required for the hypercalcemic action of the peptide.
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PMID:Uterine relaxing action of parathyroid hormone: effect of oxidation and methionine substitution. 670 44

Caprine uterine epithelial (UE) cells were cultured on Matrigel-coated filters. Transmission electron microscopy revealed polarized UE cells characterized by basally located nuclei, apical microvilli, convoluted lateral membranes, and junctional complexes. Domain-specific secretion of prostaglandins and radiolabeled proteins provide further evidence of functional epithelial cell polarity. Two experiments were conducted to evaluate factors controlling prostaglandin E2 (PGE) and prostaglandin F2alpha (PGF) secretion. In experiment one, steroid-treated (estradiol, progesterone, or estradiol + progesterone) polarized UE cells were treated with interferon tau (IFNtau) and/or oxytocin (OT). Steroid treatment did not influence PGE or PGF secretion. However, analysis of variance revealed an IFNtau by OT interaction (P < .01) for both PGE and PGF This interaction was caused by a reduction in PGE and PGF secretion by cultures receiving only IFNtau and the inability of IFNtau to block OT-induced release of PGE or PGF. In experiment 2, polarized UE cells were cultured in progesterone, with or without IFNtau, and sequentially challenged with estradiol and OT. Oxytocin stimulated the release of both PGE and PGF by polarized cUE cells (P < .01) and resulted in an increased accumulation of PGE (OT*domain; P < .01) in the basal compartment. Interferon tau did not influence PGE (P < .1) secretion. However, further analysis revealed that IFNtau reduced PGF secretion and was unable to block OT-induced PGF secretion (IFNtau*OT; P < .05) by polarized UE cells. Therefore, caprine UE cells form polarized monolayers and retain responsiveness to IFNtau and OT in vitro.
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PMID:Regulation of protein and prostaglandin secretion in polarized primary cultures of caprine uterine epithelial cells. 971 18

Premature delivery remains a serious risk factor in pregnancy, with currently licensed tocolytics unable to offer significant improvement in neonatal outcome. Further understanding of the regulators of uterine contractility is required to enable the development of novel and more effective tocolytic therapies. The transglutaminase family is a class of calcium-dependent, transamidating enzymes, of which tissue transglutaminase 2 is a multifunctional enzyme with roles in cell survival, migration, adhesion, and contractility. The aim of the present study was to investigate the role of this enzyme in regulating the contractility of pregnant human myometrium. Tissue strips from biopsy samples obtained at elective cesarean section were either allowed to contract spontaneously or induced to contract with oxytocin, phenylephrine, or bradykinin. Activity integrals, used to measure contractile activity, were taken following cumulative additions of the reversible, polyamine transglutaminase inhibitors cystamine and mono-dansylcadaverine and the irreversible, site-specific transglutaminase inhibitors N-benzyloxycarbonyl-l-phenylalanyl-6-dimethylsulfonium-5-oxo-L-norleucine and 1,3-dimethyl-2[(oxopropyl)thio]imidazolium. The ability of cystamine and mono-dansylcadaverine to affect oxytocin-mediated calcium mobilization within primary cultured myometrial cells was also measured utilizing a calcium indicator. All inhibitors attenuated myometrial contractions in a concentration-dependent manner independent of the method of contraction stimulus. Similarly cultured myometrial cells preincubated with cystamine and mono-dansylcadaverine displayed an altered calcium response to oxytocin stimulation. Our findings demonstrate a potential role for tissue transglutaminase 2 in regulating uterine contractility in pregnant human myometrium that may be associated with the calcium signaling cascade required for contraction.
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PMID:Inhibition of tissue transglutaminase 2 attenuates contractility of pregnant human myometrium. 2112 16