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61.
本实验利用听觉电生理学方法,研究了催产素(Oxytocin)对豚鼠内耳听觉机能的作用。给豚鼠肌内注射催产素后,由短声引起的耳蜗微音器电位和听神经复合动作电位幅值增加,听神经复合动作电位和听皮层诱发电位的阈值降低。说明催产素具有提高豚鼠内耳听觉机能的作用。 相似文献
62.
63.
Rhiannon Beard Andy Stucki Muriel Schmitt Gabrielle Py Christophe Grundschober Antony D. Gee Edward W. Tate 《Bioorganic & medicinal chemistry》2018,26(11):3039-3045
Oxytocin (OT) is an exciting potential therapeutic agent, but it is highly sensitive to modification and suffers extensive degradation at elevated temperature and in vivo. Here we report studies towards OT analogs with favorable selectivity, affinity and potency towards the oxytocin receptor (OTR), in addition to improving stability of the peptide by bridging the disulfide region with substituted dibromo-xylene analogs. We found a sensitive structure-activity relationship in which meta-cyclized analogs (dOTmeta) gave highest affinity (50?nM Ki), selectivity (34-fold), and agonist potency (34?nM EC50, 87-fold selectivity) towards OTR. Surprisingly, ortho-cyclized analogs demonstrated OTR and vasopressin V1a receptor subtype affinity (220?nM and 69?nM, respectively) and pharmacological activity (294?nM and 35?nM, respectively). V1a binding and selectivity for ortho-cyclized peptides could be improved 6-fold by substituting a neutral residue at position 8 with a basic amino acid, providing potent antagonists (14?nM IC50) that displayed no activation of the OTR. Furthermore, xylene-bridged analogs demonstrated increased stability compared to OT at elevated temperature, demonstrating promising therapeutic potential for these analogs which warrants further study. 相似文献
64.
Summary Immunoreactive galanin-like material was recently shown to co-exist with vasopressin in parvocellular and magnocellular perikarya of the paraventricular nucleus in the anterior hypothalamus of the rat (Melander et al. 1986). Since this distribution pattern differed from our observation of oxytocin-associated galanin-like immunoreactivity (LI) in the neurohypophysis, we compared in series of 0.5-m thick sections the localisation of galanin-LI with the localisation of oxytocin and vasopressin/dynorphin in the hypothalamus, the median eminence and the neurohypophysis. In the oxytocin system, galanin-LI was intense in oxytocin varicosities of the neurohypophysis. Oxytocin perikarya of the hypothalamic supraoptic and paraventricular nuclei exhibited galanin-LI only after intraventricular injection of colchicine and when sections were treated with trypsin prior to application of the antibody. In the vasopressin/dynorphin system galanin-LI was intense in hypothalamic perikarya after colchicine injection and in neurohypophysial varicosities after treatment of the sections with trypsin. In these neurones, galanin-LI was absent or weak in all elements when treatments with colchicine or trypsin were omitted. Galanin-LI in the neurohypophysis was not co-localised with the numerous fine endings showing GABA-LI. These observations indicate that galanin-like material coexists with vasopressin and oxytocin in the respective magnocellular neurones, although not always in an immunoreactive form. 相似文献
65.
A steric parameter (Yγ) has been derived for α-amino acids to characterize the steric hindrances near to the α-carbon atom. This easily computable variable is suitable for quantitative structure-activity relationship (QSAR) calculations for peptide hormones. Successful multivariate analyses were performed for oxytocin and angiotensin II analogs with the help of parameters describing the lipophilic and steric properties and the measure of dispersion forces. In the case of position 4 substituted oxytocin analogs, the steric, lipophilic and H-bridge forming properties equally account for the different biological activities of the derivatives. In the case of position 5 substituted angiotensin II analogs, primarily the steric parameters account for the biological activity of the series of derivatives. 相似文献
66.
Quantitation of Vasopressin mRNA and Oxytocin mRNA in Hypothalamic Nuclei by Solution Hybridization Assays 总被引:1,自引:0,他引:1
J. Peter H. Burbach Hubert H. M. Van Tol Marleen H. C. Bakkus Hartwig Schmale Richard Ivell 《Journal of neurochemistry》1986,47(6):1814-1821
Concentrations of vasopressin (VP) precursor and oxytocin (OT) precursor mRNA were measured in magnocellular cell groups of the rat hypothalamus by newly developed solution hybridization assays. The assays employed single-stranded 35S-labeled VP-specific and OT-specific DNA probes that were prepared by primer extension on recombinant M13 DNA templates. Solution hybridization assays were standardized by known amounts of cloned DNA. The detection limit was less than 1 pg DNA equivalent of the respective mRNA. In total RNA preparations of microdissected supraoptic nucleus (SON) mean (+/- SEM) basal levels of 1.37 +/- 0.18 pg VP mRNA and 1.95 +/- 0.14 pg OT mRNA were measured. RNA of the microdissected paraventricular nucleus (PVN) contained 0.35 +/- 0.02 pg VP mRNA and 1.77 +/- 0.15 pg OT mRNA. Elevation of plasma osmolality induced by drinking of 2% saline for 25 days resulted in a 1.85-fold increase in VP mRNA levels of the SON and a 1.6-fold increase in VP mRNA levels of the PVN. The solution hybridization assays are suitable tools to study the regulation of VP and OT mRNAs in magnocellular neurons of the brain. 相似文献
67.
Summary In adrenalectomized rats the influence of salt loading or salt deprivation on the vasopressin and oxytocin content of the median eminence (ME) and the neural lobe (NL) was studied by means of various methods: (1) morphometric and microphotometric analysis of aldehyde fuchsin-stained sections of ME and NL; (2) immunohistochemical demonstration of neurophysin, oxytocin, and vasopressin in the ME and in the NL; (3) radioimmunological measurement of oxytocin and vasopressin in the ME and in the NL. Adrenalectomy in salt-substituted rats raised the vasopressin content of the outer layer of the ME (OLME) but had no influence on the amount of vasopressin in the inner layer of the ME and in the NL. Osmotic stimulation of adrenalectomized rats by hypertonic saline markedly diminished vasopressin and oxytocin in the inner layer of the ME and in the NL but did not, or only slightly reduced vasopressin in the OLME. Withdrawal of salt supplementation in adrenalectomized rats resulted in a decrease of plasma sodium and plasma volume. It did not change the vasopressin or oxytocin content of the inner layer of the ME and of the NL, but it was correlated with a decrease of vasopressin in the OLME. The present findings may suggest that vasopressin in the OLME is involved in salt and/or volume regulation by influencing the hypophysial-adrenal axis.The study was supported by the Deutsche Forschungsgemeinschaft (Bo 392/6-51 and SFB 90, Cardiovasculäres System, A52). The morphometric measurements with the TAS plus were carried out at the Max-Planck-Institut für Psychiatrie, Munich, FRG. We are particularly indebted to Prof. G. W. Kreutzberg and Prof. P. Schubert for their help 相似文献
68.
Summary Vasopressin and oxytocin were specifically demonstrated in the rat brain using the unlabelled antibody-enzyme method and purification of the first antiserum. Vasopressin and oxytocin fibres extend via the subcommissural organ or habenular commissure into the pineal stalk and terminate in the anterior part of the pineal organ. In addition, immediately adjacent to the subsommissural organ many vasopressin-containing fibres run caudally toward the central grey. These results are discussed in relation to the proposed presence of vasotocin in the pineal gland.This study was supported by the Foundation for Medical Research, FUNGOThe authors wish to thank Dr. D.F. Swaab and Prof. J. Ariëns Kappers for their suggestions and critical remarks 相似文献
69.
In Experiment 1, blood samples were collected on days 1, 4, 7, 10, 13, 16, 19, 22, and 25 postpartum from the jugular veins of 10 suckled beef cows to determine 13, 14-dihydro-15-keto prostaglandin F(2)alpha (PGFM) concentrations during the early postpartum period. PGFM concentrations on days 1 and 4 were 207.8 +/- 33.9 and 283.6 +/- 45.6 pg/ml and then declined linearly (r = -0.71; P < 0.05) to 44.1 +/- 5.7 and 44.0 +/- 5.3 pg/ml on days 22 and 25 postpartum. Two groups of postpartum (25.3 +/- 0.5 and 37.7 +/- 1.1 days) suckled beef cows (10 cows/group) were used in the second experiment. Five cows of each group received intrauterine infusions of indomethacin for 5.5 days while the other five cows of each group served as controls. All cows had calves removed at the time of the last indomethacin infusion and were subcutaneously administered oxytocin six hours later. During the infusion period, PGFM concentrations decreased (P < 0.01) across time for both groups of indomethacin-treated cows. Concentrations of PGFM increased (P < 0.05) after oxytocin treatment for both groups of control and indomethacin-treated cows, but concentrations were higher for the control cows than for the indomethacin-treated cows. 相似文献
70.
Vasopressin and oxytocin cause behavioral excitation after intracerebroventricular injection in mice. This effect is short-lasting, suggesting that the peptides are rapidly inactivated in the brain. Co-injection of microgram amounts of amastatin, an aminopeptidase inhibitor, prolonged the effect of both vasopressin and oxytocin. Amastatin did not induce large vasopressin-like behavioral effects by itself, nor did it significantly potentiate the action of 1-deamino[1,6-dicarba, 8-arginine] vasopressin (Asu-AVP), an analog that lacks the N-terminal amino group. The effect of Asu-AVP, but not that of vasopressin, was potentiated by phosphoramidon, an inhibitor of neutral metalloendopeptidase ("enkephalinase A"). These results support previous suggestions that vasopressin and oxytocin are inactivated mainly by aminopeptidase action following intracerebroventricular injection. 相似文献