Oxytocin antagonists delay the initiation of parturition and prolong its active phase in rats

Antonijevic, Irina A.; Douglas, Alison J.; Dye, S.; Bicknell, R.J.; Leng, Gareth; Ja, Russell

doi:10.1677/joe.0.1450097

Cited by 61 publications

(35 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, there is significant increase in uterine sensitivity to OT via upregulation of OTR in both rats and humans during the onset of labour [12][13][14]. Additionally studies in rats [15][16][17], non-human primates [18][19][20] and in humans [21,22] reported that OT antagonists can inhibit late gestational uterine contractions and the process of parturition. The role of OT varies between different animal species.…”

Section: Previously Established Roles Of Ot/otr Systemmentioning

confidence: 99%

Advances in the role of oxytocin receptors in human parturition

Kim

Bennett

Terzidou

2017

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Section: Previously Established Roles Of Ot/otr Systemmentioning

confidence: 99%

Advances in the role of oxytocin receptors in human parturition

Kim

Bennett

Terzidou

2017

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

“…It is high relevant between premature delivery and oxytocin, QSAR study on oxytocin peptides and homologous antagonist design are both valuable in theories and the applications to premature delivery. [23][24] A set of 21 oxytocin peptides was also used to test the descriptors predictability, their bioactivities scales were intensity uterine contraction of mice. 25 Each oxytocin peptide contains 3 amino acids, and the structural information of each peptide was quantified by 24 variables.…”

Section: Qsar Analysis On Oxytocin Peptidesmentioning

confidence: 99%

Predicting the Activity of Peptides Based on Amino Acid Information

Wang

et al. 2011

J Chinese Chemical Soc

View full text Add to dashboard Cite

A set of amino acid descriptors including hydrophobic, stereo and electrical properties were applied to construct quantitative structure-activity relationships (QSARs) models of three peptides datasets (angiotensin-converting enzyme inhibitor dipeptides, bactericidal peptides and oxytocin peptides) with stepwise multiple regression combined partial least squares regression (SMR-PLS). The results of QASRs models are very robust, with multiple correlation coefficients (R 2 ), and cross validation (Q 2 ) equal to 0.687, 0.671; 0.977, 0.890 and 0.950, 0.802 respectively. The robust models show the descriptors can be further expanded for polypeptides and serve as a useful quantitative tool for the rational drug design and discovery.Keywords: Quantitative structure-activity relationship; Peptides; Stepwise multiple regression; Partial least squares regression. INTRODUCTIONPeptides play an important role in all living systems. They act as hormones, enzyme substrates, inhibitors, neurotransmitters and immunomodulating agents, which are driving considerable pharmacological interest in design and application of new drugs. 1 Quantitative structure-activity relationships (QSARs) has been brought into the spotlight, which is involved in pharmaceutical chemistry, pharmacology and the foundation of drug design. The nature of QSAR is to express the relation of structural features and biological activities. If the relationship between the peptide structures and biological activities can be confirmed, a large amount of peptide drugs will be successfully synthesized on this basis. [2][3] In the 1960s, Sneath et al. first expressed peptide sequences by using semi-quantitative experimental 55 parameters of 20 coded amino acids and successfully predicted the activities of hypophamine. 4 Kidera et al collected 188 properties of the 20 natural amino acids and employed factor analysis to obtain 10 orthogonal factors which determined three dimensional structures of proteins. 5 Hellberge et al used principal component analysis (PCA) for 29 physicochemical properties to each of 20 natural amino acids, including electrostatic, stereo and hydrophobic properties, which were respectively encoded as Z 1 , Z 2 and Z 3 . 6-8 Z-scales was obtained and it has proven to be an useful descriptor for short peptides modeling. Based on the three dimensional descriptors, isotropic surface area (ISA) and electronic charge index (ECI), Collantes et al established good 3D-QSAR models. 9 As QSARs study have advanced, a series of descriptors were proposed, which can well represent the structural characterization of amino acids for QSAR models, such as MS-WHIM, MARCH-IN-SIDE, VHSE, T-scales, VSW, V, HESH and ST-scale etc. [10][11][12][13][14][15][16][17][18] Almost all the descriptors mentioned above were derived from the principal component analysis (PCA) of the data matrixes, which may cursorily explained physicochemical properties of amino acids, such as hydrophobicity, molecular volume, net charge etc. Each principal component is a linear combination to the...

show abstract

“…During parturition, one-third of oxytocin stores in the pituitary are depleted (Fuchs & Saito 1971), and if oxytocin function is impaired, parturition is slowed or ceases completely (Antonijevic et al 1995a(Antonijevic et al , 2000. In mice and rats, treatment with an oxytocin antagonist slows parturition, while exogenous oxytocin treatment during impaired parturition can rescue normal parturition (Antonijevic et al 1995b, Douglas et al 2002.…”

Section: Introductionmentioning

confidence: 99%

Intracerebroventricular administration of the prolactin (PRL) receptor antagonist, S179D PRL, disrupts parturition in rats

Nephew

Amico²,

Cai³

et al. 2007

Reproduction

View full text Add to dashboard Cite

The prolactin (PRL) receptor antagonist S179D PRL delays the onset of maternal behavior in steroid-primed nulliparous female rats. The present study investigated the role of the neural PRL system in the process of parturition. A preliminary study indicated that S179D PRL treatments administered by ALZET minipump to the lateral ventricle severely disrupted parturition. To examine the likely causes of this disruption, a group of timed-pregnant catheterized rats was continuously infused with S-179D PRL (0.001 and 0.1 ng/h) or vehicle control to the lateral ventricles for 3 days (gestation days 21-23), and serial blood samples were taken throughout this period. Effects of the treatments on parturition were recorded, and blood samples were assayed for PRL, progesterone, and oxytocin. Significantly fewer S179D PRL-treated rats successfully delivered by 1500 h on day 23 of gestation when compared with controls. The higher dose of S179D PRL also significantly suppressed the prepartum rise in PRL throughout the prepartum period, while the lower dose only affected plasma PRL during the first 24 h of treatment. No significant effects of the antagonist on plasma progesterone or oxytocin were detected. We conclude that disruption of parturition by S179D PRL is not caused by significant alterations in the plasma concentrations of progesterone or oxytocin. S179D PRL may indirectly act on parturition through the modulation of prepartum PRL. These findings suggest a previously unrecognized role for PRL in the regulation of parturition. Reproduction (2007) 134 155-160

show abstract

Oxytocin antagonists delay the initiation of parturition and prolong its active phase in rats

Cited by 61 publications

References 0 publications

Advances in the role of oxytocin receptors in human parturition

Advances in the role of oxytocin receptors in human parturition

Predicting the Activity of Peptides Based on Amino Acid Information

Intracerebroventricular administration of the prolactin (PRL) receptor antagonist, S179D PRL, disrupts parturition in rats

Contact Info

Product

Resources

About