Smooth muscle electromyography for detecting major alterations in the estrus cycle in rats.

Determining the female animal cycle is crucial in preclinical studies and animal husbandry. Changes in hormone levels during the cycle affect physiological responses, including altered contractility of the visceral smooth muscle. The study aimed to identify estrus and anestrus using smooth muscle electromyographic (SMEMG) measurements, in vivo fluorescent imaging (IVIS) and in vitro organ contractility of the uterus and cecum.

Non-genomic uterorelaxant actions of corticosteroid hormones in rats: An in vitro and in vivo study.

Aims: We aimed to identify the short-term effects of a glucocorticoid (GC) and a mineralocorticoid (MC) on non-pregnant and late pregnant rat uterine contractions to estimate their tocolytic potential.

Methods: The in vitro contractility studies were performed with uterine tissues from non-pregnant and 22-day pregnant SPRD rats. The cumulative dose-response of fludrocortisone (FLU) and dexamethasone (DEX) was measured alone or in the presence of steroid receptor antagonist mifepristone (MIF) or spironolactone (SPR).

High Fat High Sucrose Diet Modifies Uterine Contractility and Cervical Resistance in Pregnant Rats: The Roles of Sex Hormones, Adipokines and Cytokines.

Background: In obesity, the adipose tissue becomes a very significant endocrine organ producing different factors called adipokines, such as leptin, adiponectin and kisspeptin; however, no data are available about their actions on uterine contraction in obese pregnant rats. Our aim was to study the impact of obesity on pregnant uterine contraction in a rat model.

Methods: Obesity was induced by the consumption of a high fat high sucrose diet (HFHSD) for 9 weeks, including pregnancy.

Synthesis of 1-(-methoxyphenyl)tetrazolyl-Substituted 1,2,3,4-Tetrahydroisoquinolines and Their Transformations Involving Activated Alkynes.

1-(-Methoxyphenyl)tetrazolyl-substituted 6,7-dimethoxy(6,7-methylenedioxy)-1,2,3,4-tetrahydroisoquinolines formed tetrazolyl-substituted azocines in high yields by using activated alkynes. Unsubstituted at 6,7,8-aromatic fragment 1-tetrazolylisoquinoline interacted in several pathways forming tetrazolyl-substituted azocines, 1-tetrazolyl-1-R-vinylisoquinolines and 3-azaspiro[5.5]undeca-1,7,9-triene.

The effect of increased NaCl intake on rat brain endogenous μ-opioid receptor signalling.

Numerous studies demonstrate the significant role of central β-endorphin and its receptor, the μ-opioid receptor (MOR), in sodium intake regulation. The present study aimed to investigate the possible relationship between chronic high-NaCl intake and brain endogenous MOR functioning. We examined whether short-term (4 days) obligatory salt intake (2% NaCl solution) in rats induces changes in MOR mRNA expression, G-protein activity and MOR binding capacity in brain regions involved in salt intake regulation.

A new approach to alkaloid-like systems: synthesis and crystal structure of 1-(2-acetyl-11-meth-oxy-5,6-di-hydro-[1,3]dioxolo[4,5-]pyrrolo-[2,1-]isoquinolin-1-yl)propan-2-one.

The title compound, CHNO, (I), is the product of a domino reaction between cotarnine chloride and acetyl-acetylene catalysed by copper(I) iodide. The mol-ecule of (I) comprises a fused tetra-cyclic system containing two terminal five-membered rings (pyrrole and 1,3-dioxole) and two central six-membered rings (di-hydro-pyridine and benzene). The five-membered 1,3-dioxole ring has an envelope conformation and the central six-membered di-hydro-pyridine ring adopts a twist-boat conformation.

Herbal laxatives and antiemetics in pregnancy.

Constipation appears in the 2nd and 3rd trimester of pregnancy, while nausea is the strongest in the 1st trimester. This review summarizes the applicability of herbal laxatives and antiemetics in pregnancy. A human study has shown that flax oil as laxative is safe from 2nd trimester.

Kynurenic acid and its analogue can alter the opioid receptor G-protein signaling after acute treatment via NMDA receptor in rat cortex and striatum.

Previously, we have shown that the N-methyl d-aspartate (NMDA)-receptor antagonist kynurenic acid (KYNA) and its analogue KYNA1 do not bind directly to mu, kappa and delta opioid receptors in vitro. On the other hand, chronic administration of KYNA and KYNA1 resulted in region (cortex vs striatum) and opioid receptor-type specific alterations in G-protein activation of mouse brain homogenates. Here we describe for the first time the acute effect of KYNA and KYNA1 on opioid receptor function with the possible involvement of the NMDA receptor.

Identification of myoelectric signals of pregnant rat uterus: new method to detect myometrial contraction.

Aim: To develop an electromyography method for pregnant rat uterus in vivo and to separate myometrial signals from the gastrointestinal tract signals.

Methods: Pregnant Sprague-Dawley rats (n=8) were anaesthetized and their stomach, small intestine, and large intestine were removed from the abdomen. A pair of thread electrodes was inserted into the uterus, while a pair of disk electrodes was placed subcutaneously above the myometrium.

Obesity in pregnancy: a novel concept on the roles of adipokines in uterine contractility.

Obesity is a global health problem even among pregnant women. Obesity alters quality of labor, such as preterm labor, prolonged labor, and higher oxytocin requirements in pregnant women. The most important factors to play a role in the altered gestational period and serve as drug targets to treat the consequences are female sexual hormones, calcium channels, adrenergic system, oxytocin, and prostaglandins.

Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors.

Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH.

The effects of progesterone on the alpha2-adrenergic receptor subtypes in late-pregnant uterine contractions in vitro.

Background: The adrenergic system and progesterone play major roles in the control of the uterine function. Our aims were to clarify the changes in function and expression of the α2-adrenergic receptor (AR) subtypes after progesterone pretreatment in late pregnancy.

Methods: Sprague Dawley rats from pregnancy day 15 were treated with progesterone for 7 days.

The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro.

Aim: To assess the effect of 17β-estradiol pretreatment on the function and expression of α2- adrenergic receptors (ARs) subtypes in late pregnancy in rats.

Methods: Sprague-Dawley rats (n=37) were treated with 17β-estradiol for 4 days starting from the 18th day of pregnancy. The myometrial expression of the α2-AR subtypes was determined by real time polymerase chain reaction and Western blot analysis.

Evaluation of the analgesic effect of 4-anilidopiperidine scaffold containing ureas and carbamates.

Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs.

The effects of female sexual hormones on the expression and function of α1A- and α1D-adrenoceptor subtypes in the late-pregnant rat myometrium.

The aim of the study was to investigate the roles of α1-adrenoceptor subtypes in the last-day pregnant rat uterus in vitro by the administration of subtype-specific antagonists (the α1A-adrenoceptor antagonist WB 4101 and the α1D-adrenoceptor antagonist BMY 7378) after 17β-estradiol or progesterone pretreatment. In isolated organ bath studies, contractions were elicited with (-)-noradrenaline (10(-8)-10(-5)M) in the presence of propranolol (10(-5)M) and yohimbine (10(-6)M) in order to avoid β-, and α2-adrenergic action. The myometrial expressions of the α1-adrenoceptor subtypes were determined by means of the real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting techniques.

Inhibition of opioid receptor mediated G-protein activity after chronic administration of kynurenic acid and its derivative without direct binding to opioid receptors.

There is an increasing number of evidence showing analgesic properties of the kynurenic acid (KYNA), and also some studies demonstrate that kynurenine might interact with the opioid system. Therefore in this study, for the first time we investigated the direct binding affinity of KYNA and its structural analog KYNA-1 towards mu, kappa and delta opioid receptor in competition binding experiments applying opioid receptor specific radioligands. The binding affinity measurements were performed in Chinese hamster ovary cell lines overexpressing the corresponding opioid receptor (mu and kappa opioid receptor were rat, delta opioid receptor were mouse sequence).

Low dosage of rimonabant leads to anxiolytic-like behavior via inhibiting expression levels and G-protein activity of kappa opioid receptors in a cannabinoid receptor independent manner.

What Is Known: There is an increasing number of studies demonstrating the direct effect of the cannabinoid receptor 1 (CB1) antagonist/inverse agonist rimonabant on the opioid system. The kappa opioid receptors (KORs) are well known to mediate depression- and anxiety-like behavior. Clinical studies on chronic rimonabant administration have revealed that rimonabant leads to a very similar pathophysiology, suggesting a potential impact of rimonabant on KORs.

Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav 2.2 Blocker Multitarget Ligands.

N-type voltage-dependent Ca(2+) channels (CaV 2.2) are located at nerve endings in the central and peripheral nervous systems and are strongly associated with the pathological processes of cerebral ischaemia and neuropathic pain. CaV 2.

Novel cyclic biphalin analogue with improved antinociceptive properties.

Two novel opioid analogues have been designed by substituting the native d-Ala residues in position 2,2' of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent μ/δ mixed receptor affinities (K i (δ) = 5.2 nM; K i (μ) = 1.