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)

1 Synthetic analogues of oxytocin and of lysine-vasopressin with an hydroxyl group in either the L ro D configuration replacing the primary amino group have been tested for biological activity.2 [1-(L-2-Hydroxy-3-mercaptopropanoic acid)] oxytocin ([L-Hmp(1)]oxytocin) was 1.5 to 2 times more potent than oxytocin on the rat uterus in situ, the rat mammary strip and the rat mammary gland in situ and 3 times more potent on the rat isolated uterus.3 The pressor activity of [1-(L-2-hydroxy-3-mercaptopropanoic acid)-8-lysine]vasopressin ([L-Hmp(1), Lys(8)] vasopressin) was 2.2 and the antidiuretic activity 2.1 times that of lysine-vasopressin.4 The [D-Hmp(1)] analogues of oxytocin and vasopressin were much less potent than the [L-Hmp(1)] analogues.5 The responses to oxytocin and its hydroxy analogues in vivo were qualitatively indistinguishable but the pressor and antidiuretic responses to the hydroxy analogues of lysine-vasopressin were prolonged compared with those to the parent hormone.6 The hydroxy analogues of oxytocin and lysine-vasopressin were not inactivated by pregnancy plasma oxytocinase.7 The results are discussed in relation to the importance of the primary amino group for the biological activity and metabolism of the neurohypophysial hormones.
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PMID:Hydroxy analogues of oxytocin and of lysine-vasopressin. 51 8

[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammonolysis and purification 1 + 8 couplings in solution were employed to furnish the required key nonapeptide and acyl octapeptide intermediates, respectively. [7-Glycine]oxytocin was prepared from a sample of the protected nonapeptide intermediate used in the original synthesis of this peptide. [7-Glycine]oxytocin has an oxytocic potency (O) of 93 +/- 4 units/mg and an antidiuretic potency (A) of 0.0056 +/- 0.0003 units/mg. It has an O/A ratio of 16 000. [4-Threonine, 7-glycine]oxytocin has an oxytocic potency of 166 +/- 4 units/mg and an antidiuretic potency of 0.002 +/- 0.0004 units/mg. Its O/A ratio is 83 000. Threonine substitution has thus brought about a substantial enhancement in oxytocic activity and a fivefold enhancement in O/A selectivity. Hydroxy [Thr4, Gly7]oxytocin has an oxytocic potency of 218 +/- 8 units/mg and antidiuretic potency of 0.0040 +/- 0.0005 units/mg. Its O/A ratio is thus 54 500. All three 7-glycine-substituted analogues exhibit a marked sensitivity to Mg2+ on the rat uterus assay ststem and in the presence of 0.5 mM Mg2+ had oxytocic potencies in the range of 900-1000 units/mg. Should these peptides exhibit enhanced oxytocic selectivity in humans, they might offer a greater margin of safety than oxytocin in those clinical stiuations in which the latter is currently employed.
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PMID:Synthesis and some pharmacological properties of [4-threonine, 7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin), and [7-Glycine]oxytocin, peptides with high oxytocic-antidiuretic selectivity. 83 10

[1-(L-2-Hydroxy-3-mercaptopropanoic acid), 4-threonine]oxytocin (hydroxy[4-Thr]oxytocin) and [1-(l-2-hydroxy-3-mercaptopropanoic acid)]oxytocin (hydroxy-oxytocin) were synthesized by a combination of solid phase and classical methods of peptide synthesis. Protected octapeptides were synthesized by the solid-phase method and 1 + 8 couplings in solution were then employed to furnish the required key protected intermediates. Hydroxy[4-Thr]oxytocin has oxytocic potency as measured in the rat uterus suspended in a Mg2+-free solution, of about 4200 units/mg, eight times the potency of oxytocin, while its antidiuretic potency is approximately equal to that of oxytocin. It thus exhibits a significantly favorable oxytocic-antidiuretic sleectivity. Hydroxy-oxytocin has an oxytocic potency of approximatels 1300 units/mt, 2.5 times that of oxytocin. Threonine substitution in hydroxy-oxytocin has thus caused a significant enhancement in both oxytocic potency and selectivity. The enhancement in oxytocic potency of these two peptides relative to oxytocin and [4-Thr]oxytocin appears to correlate with their lipophilic characteristics, suggesting a significant role of lipophilicity in the interplay of oxytocin-like peptides with oxytocic receptors.
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PMID:Synthesis and some pharmacological properties of [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine]oxytocin (hydroxy [4-thr]oxytocin), a peptide with strikingly high oxytocic potency and of [1-(L-2-hydroxy-3-mercaptopropanoic acid)]oxytocin (hydroxy-oxytocin). 94 46

16 alpha-Hydroxy-ent-kauran-19-oic acid was isolated from Montanoa hibiscifolia. The effects of this acid and its methyl ester on the contractile activity of rat and guinea pig uterine horns were studied. Both inhibited spontaneous, oxytocin-induced and potassium-induced contractile activities. The inhibitory effect produced by the methyl ester was greater than that observed with the acid. The methyl ester was 2-5 times more potent than the acid upon spontaneous and potassium-induced contractions and 11-15 times more potent than the acid upon the contractile activity of uterine smooth muscle induced by oxytocin. Such effects were observed using bath concentrations of 6, 15, 30 and 60 microM of each compound.
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PMID:The zoapatle. XV. Activity of 16 alpha-hydroxy-ent-kauran-19-oic acid isolated from Montanoa hibiscifolia, and its methyl ester on rat and guinea pig uterus. 325 83

The coding activity of bovine hypothalamic poly A+ mRNA for neurophysin I and II immunoreactive proteins was characterized with respect to size and 5' cap. The mRNA was fractionated by methylmercuric hydroxide agarose gel electrophoresis and subsequently translated in vitro in rabbit reticulocyte lysates. Alternatively, mRNA was fractionated by gel exclusion HPLC and translated in wheat germ extracts. Immunoprecipitated translation products were analyzed by gel exclusion HPLC. Neurophysin-immunospecific protein of approximately 17,000 daltons, the size expected for the neuropeptide hormone-neurophysin precursors, was encoded by mRNA species of two size classes. The smaller class of mRNA's was of the size expected from the size of the precursor proteins. The larger class was 5-10 times larger. The low K+ concentration optimum for translation of unfractionated mRNA encoding neurophysin I immunoreactive proteins and the inability of a cap analogue to inhibit this translation suggest that mRNA species encoding neurophysin I-immunoreactive translation products are incompletely capped. By contrast, the mRNA encoding neurophysin II-immunoreactive products appear to contain a normal cap structure.
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PMID:Characterization of the size and 5' cap of messenger RNA encoding neurophysin precursors. 614 45

In order to investigate the role of central GABAB receptors in the control of the milk ejection reflex, we have examined the effects of third ventricular and bilateral supraoptic nucleus (SON) injections of a GABAB receptor agonist (baclofen) and antagonist (hydroxy-saclofen) on the milk ejection reflex in the urethane-anaesthetised rat. In addition, microdialysis studies have evaluated whether the activation of GABAB receptors in the SON is able to modulate the release of GABA and glutamate, two major neurotransmitters involved in the regulation of the milk ejection reflex. Intracerebroventricular injections of baclofen (n = 9) in doses of 10, 50 and 100 pmol inhibited the milk ejection reflex in a dose-dependent manner, without affecting the electroencephalogram or attenuating the intramammary pressure response to intravenous injection of 0.5 mU exogenous oxytocin. Hydroxy-saclofen given into the third ventricle in doses of 100 pmol (n = 2) and 500 pmol (n = 4) did not modify the pattern of the milk ejection reflex. Bilateral SON microinfusions of baclofen in doses of 80 (n = 2) and 200 pmol (n = 4) did not modify the pattern of the milk ejection reflex. In microdialysis experiments (n = 8), inclusion of baclofen into the microdialysate at a concentration of 500 microM had no effect upon basal or potassium-stimulated GABA and glutamate outflow. These results show that the activation of GABAB receptors located outside, but not within, the SON are capable of inhibiting the milk ejection reflex. In contrast to our previous findings regarding the GABAA receptor, we found no evidence for a tonic role of GABAB receptors within the neural network inducing the periodic synchronous bursting of oxytocin neurons during suckling.
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PMID:Effects of central GABAB receptor modulation upon the milk ejection reflex in the rat. 873 92