Effects of newly synthetized isoquinoline derivatives on rat uterine contractility and ROCK II activity.

Protein kinases have an important role in signal transduction in the cellular system via protein phosphorylation. RhoA activated Rho-kinases have a pivotal role in the regulation of smooth muscle contraction. ROCK I and ROCK II phosphorylate myosin-phosphatase and myosin-kinase, which induces contraction in the myometrium.

Alteration in expressions of RhoA and Rho-kinases during pregnancy in rats: their roles in uterine contractions and onset of labour.

Activation of RhoA and Rho-associated kinases (ROCKs) is known to play a pivotal role in the regulation of smooth muscle contraction via phosphorylation of myosin-light chain and myosin phosphatase. There are few data on the RhoA and ROCKs expression levels in rat uteri. Therefore, our aim was to investigate the mRNA and protein concentration of RhoA and ROCKs in rat uterus during pregnancy, during parturition and post-partum using real time PCR and Western blot analysis.

The Effects of Female Sexual Hormones on the Expression of Aquaporin 5 in the Late-Pregnant Rat Uterus.

Thirteen mammalian aquaporin (AQP) water channels are known, and few of them play a role in the mammalian reproductive system. In our earlier study, the predominance of AQP5 in the late-pregnant rat uterus was proven. Our current aim was to investigate the effect of estrogen- and gestagen-related compounds on the expression of the AQP5 channel in the late-pregnant rat uterus.

Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats.

The aim of this investigation was to compare the effectiveness of long-term pretreatment with amiodarone (AMIO) and its active metabolite desethylamiodarone (DEA) on arrhythmias induced by acute myocardial infarction in rats. Acute myocardial infarction was induced in conscious, male, Sprague-Dawley rats by pulling a previously inserted loose silk loop around the left main coronary artery. Long-term oral pretreatment with AMIO (30 or 100 mg·(kg body mass)(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days) or DEA (15 or 50 mg·kg(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days), was applied for 1 month before the coronary artery occlusion.

ATP-sensitive potassium channels modulate in vitro tocolytic effects of β₂-adrenergic receptor agonists on uterine muscle rings in rats in early but not in late pregnancy.

Aim: To investigate whether ATP-sensitive potassium (K(ATP)) channels modulate the tocolytic effect of β2-adrenergic receptor (β2-AR) agonists (ritodrine and salmeterol) in early-pregnant (day 6) and late-pregnant (day 22) rat uterus in vitro, in order to examine the relation between the K(ATP) channel sulphonylurea-binding regulatory subunit (SUR) expression and pharmacological reactivity of β2-AR agonists.

Methods: The tocolytic effects of ritodrine and salmeterol (10(-10)-10(-5) M) on spontaneous rhythmic contractions were investigated cumulatively, alone, or in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M) and the K(ATP) channel opener pinacidil (10(-9)-10(-7) M) after 5-min preincubation.

Results: β2-AR agonist induced myometrial relaxation was inhibited by glibenclamide and enhanced by pinacidil on day 6, when SUR1 expression levels were high.

Oxytocin regulates the expression of aquaporin 5 in the late-pregnant rat uterus.

Aquaporins (AQPs) are integral membrane channels responsible for the transport of water across a cell membrane. Based on reports that AQPs are present and accumulate in the female reproductive tract late in pregnancy, our aim was to study the expression of AQP isoforms (AQP1, 2, 3, 5, 8, and 9) at the end of pregnancy in rat in order to determine if they play a role in parturition. Reverse-transcriptase PCR revealed that specific Aqp mRNAs were detectable in the myometrium of non-pregnant and late-pregnancy (Days 18, 20, 21, and 22 of pregnancy) rat uteri.

[Khat (Catha edulis): is it "coffee" or "cocaine"?].

Regular consumption of khat's (Catha edulis) fresh leaves seriously affects the health, the social and economic life of the subject. Therefore, it is hazardous both to the individual and to the community. According to the latest reports, consumption of chat may exert some unknown and unreported gastrointestinal and hepatic effects.

Nocistatin inhibits pregnant rat uterine contractions in vitro: roles of calcitonin gene-related peptide and calcium-dependent potassium channel.

The endogenous neuropeptide nociceptin/orphanin FQ, translated from the prepronociceptin gene, exerts a contraction-inhibitory effect on the rat uterus. As nocistatin has been reported to cause functional antagonism of the pro-nociceptive effects of nociceptin, we set out to investigate its effects on the pregnant rat uterus and to elucidate its signalling pathway. The expression of prepronociceptin mRNA in the uterus and nocistatin levels in the uterus and the plasma were confirmed by RT-PCR and radioimmunoassay.

Increase of the uterus-relaxant effect of nifedipine by the Abcg2 efflux protein inhibitor KO134 in the rat in vivo.

Background/aim: High Abcg2 (ATP-Binding Cassette Transporter Subfamily G, Member-2) levels have been found in reproductive tissues, such as the placenta and uterus. The substrate specificity of Abcg2 is very wide, including uterus-relaxant agents (e.g.

Uterus-relaxing effect of β2-agonists in combination with phosphodiesterase inhibitors: studies on pregnant rat in vivo and on pregnant human myometrium in vitro.

Aims: Our aims were to examine the effects of a simultaneous stimulation of β(2) -adrenergic receptors and inhibition of uterine phosphodiesterases (PDE), in the pregnant rat uterus in vivo and on human uterine tissue in vitro. We also set out to measure cAMP levels and detect the expressions of the isoenzymes PDE4B and PDE4D in human uterine tissue samples.

Material And Methods: Preterm birth was induced in Sprague-Dawley rats with bacterial lipopolysaccharide.

Antiproliferative effect of normal and 13-epi-D-homoestrone and their 3-methyl ethers on human reproductive cancer cell lines.

The possibility of the therapeutic use of estrogens emerged following the recognition that certain estradiol analogs, and particularly metabolites (e.g. the A-ring metabolite 2-hydroxyestrone, etc.

Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro.

Inhibition of the local formation of estrogens seems to be an attractive strategy for pharmacological intervention in hormone-dependent disorders. The direct antiproliferative properties of ten nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors were investigated on human cancer cell lines of gynecological origin. The mechanism of the antiproliferative action was approximated by cell cycle analysis, fluorescent microscopy, BrdU assay, determination of caspase-3 activity and quantification of the expression of cell cycle regulators at mRNA level.

[Ontogeny of sulphonylurea-binding regulatory subunits of K(ATP) channels in the pregnant rat myometrium].

K(ATP) channels are composed of sulphonylurea receptors (SURs) and potassium inward rectifiers (Kir(6.x)) that assemble to form a large octameric channel. This study was designed to examine the expression and role of sulphonylurea-binding regulatory subunits 1 [SUR1 (ABCC8)] and 2 [SUR2 (ABCC9)] of the K(ATP) channels in the pregnant rat myometrium with particular regard to the contractility.

β(2)-Adrenergic activity of 6-methoxykaempferol-3-O-glucoside on rat uterus: in vitro and in silico studies.

6-Methoxykaempferol-3-O-glucoside (6-MKG) was isolated from a Sudanese herb (El-hazha). The pharmacological effects of 6-MKG were tested on isolated non-pregnant or late-pregnant rat uteri in vitro, whilst docking studies were carried out modelling of the binding of 6-MKG to the rat β(2)-adrenoceptor in silico. In vitro studies revealed that 6-MKG was able to relax both the non-pregnant and the late-pregnant uterine contractility with 50% of the E(max) of terbutaline, whilst the EC(50) for 6-MKG was at least half than that of terbutaline.

Ontogeny of sulfonylurea-binding regulatory subunits of K(ATP) channels in the pregnant rat myometrium.

ATP-sensitive potassium channels (K(ATP) channels) are composed of sulfonylurea receptors (SURs) and potassium inward rectifiers (Kir(6.x)) that assemble to form a large octameric channel. This study was designed to examine the expression and role of sulfonylurea-binding regulatory subunits 1 (SUR1 (ABCC8)) and 2 (SUR2 (ABCC9)) of the K(ATP) channels in the pregnant rat myometrium with particular regard to the contractility.

[Investigation of uterus-relaxing effects of nifedipine in the presence of terbutaline and K(+)-channel blockers].

Unlabelled: Tocolysis is one of the greatest challenges in obstetrical practice. It is known that the calcium channel antagonists abolish the intracellular calcium ion transients and myometrial contraction. However there is a growing interest in experimental studies to use different tocolytic combination.

The effects of adjuvant arthritis on the myometrial adrenergic functions in the nonpregnant and the late-pregnant rat.

The beneficial effects of pregnancy on the symptoms of inflammatory diseases are well documented. The modulation in the uterine functions in the presence of generalized inflammation, however, is much less characterized. The aim of the present study was to explore the modulatory action of adjuvant arthritis on the adrenergic functions of the uterus in nonpregnant and late pregnant rats.

Improving the relaxing effect of terbutaline with phosphodiesterase inhibitors: studies on pregnant rat uteri in vitro.

Aims: Previous results by our group showed that the in vitro uterus-relaxing potency of β(2)-adrenergic receptor (β(2)-AR) agonists and uterine cAMP accumulation are enhanced in case of visceral inflammation. Our aim was to study the effects of the non-selective phosphodiesterase (PDE) inhibitor theophylline and the selective PDE4 inhibitor rolipram on the uteri of intact late-pregnant female rats (on days 20 and 22 of pregnancy) and of pregnant rats treated with lipopolysaccharide (LPS) to evoke preterm labor (on day 20).

Main Methods: The effects of theophylline and rolipram alone and of rolipram with terbutaline were investigated in isolated organ system.

Potentiation of the uterus-relaxing effects of β-adrenergic agonists with nifedipine: studies on rats and the human myometrium.

Objective: We investigated how progesterone and salmeterol modify the effect of nifedipine in an in vivo preterm birth model in rats, and how terbutaline and nifedipine modify the contractions of the isolated human myometrium.

Design: Experimental animal and human myometrial studies.

Sample: Twenty-four female Sprague-Dawley rats and 13 human uterine tissues sampled from cesarean section.

Nociceptin inhibits uterine contractions in term-pregnant rats by signaling through multiple pathways.

The actions of the endogenous peptide nociceptin (PNOC; previously abbreviated as N/OFQ) on the myometrium have not been investigated previously. Our aim was to study the presence and functional role of PNOC in the modulation of uterine contractility in pregnant rats at term. The presence of PNOC and its receptors (OPRL1; previously called NOP) in the uterus were detected by radioimmunoassay and radioligand-binding experiments.

[Thermoanalytical investigation of rat myometrium during gestation].

The aim of our present study was the investigation of rat myometrium by means of differential scanning calorimetry as a function of gestational age. Some additional groups of animals were exposed to adjuvant arthritis as a model for generalized inflammation. In order to find a connection between calorimetrically determined parameters and motor activity isolated organ experiments were performed and spontaneous as well as KCl-stimulated contractility were recorded.

Khat - a controversial plant.

Khat (Catha edulis) is a shrub or tree whose leaves have been chewed for centuries by people who live in the Eastern part of Africa and the Arabian Peninsula. It has recently turned up in North America and Europe, particularly among emigrants and refugees from countries such as Somalia, Ethiopia and Yemen. Khat contains a number of chemicals, among which are two controlled substances, cathinone (Schedule I) and cathine (Schedule IV).

Modification of the effect of nifedipine in the pregnant rat myometrium: the influence of progesterone and terbutaline.

Aims: The aims of the study were to investigate the effects of nifedipine on potassium chloride (KCl)-evoked rat uterine contractions on different days of pregnancy in vitro, and the alterations in the effects of nifedipine on combination with terbutaline or progesterone.

Main Methods: In rat myometrial rings taken on different days of pregnancy, rhythmic contractions were evoked with KCl in an isolated organ bath.

Key Findings: The relaxing effect of nifedipine was most expressed in the 25 mM KCl-induced uterine contractions, reaching the maximum on the last day of pregnancy (day 22).

[The effect of the ARC 239 on the myometrial and cervical action in the rat, in vitro].

The premature labour is one of the major challenges in the clinical practice. Finding new agents and mechanisms in the control of uterine activity is the main objective of the last decade's experiments. One of the new targets is the alpha2-adrenoceptors (alpha2-AR).

Progesterone decreases the relaxing effect of the beta3-adrenergic receptor agonist BRL 37344 in the pregnant rat myometrium.

Although the published results regarding the function of the beta(3)-adrenergic receptors (beta(3)-ARs) in the regulation of smooth muscle activity are very promising, the question of the mechanism of beta(3)-ARs' action in the pregnant myometrium cannot be fully answered by human investigations. To assess whether it possesses an essential role in the regulation of uterine contractility in pregnant rats, as in humans, we performed functional, western blotting and molecular biology experiments on the late-pregnant rat myometrium. The influence of progesterone on the function of the beta(3)-ARs was also investigated.