Involvement of imidazoline and opioid receptors in the enhancement of clonidine-induced analgesia by sulfisoxazole.

Clonidine, an alpha2-adrenergic agonist, has been demonstrated to produce significant analgesia and potentiate morphine analgesia. Endothelin (ETA) receptor antagonists have also been found to potentiate the antinociceptive response to morphine. Clonidine and ET have been reported to have cardiovascular interactions involving the sympathetic nervous system, but it is not known whether ETA receptor antagonist affects clonidine analgesia.

Determination of adrenergic and imidazoline receptor involvement in augmentation of morphine and oxycodone analgesia by clonidine and BMS182874.

Background: Numerous agents have been demonstrated to potentiate morphine analgesia, including clonidine (alpha(2)-adrenergic and I(1)-imidazoline receptor agonist) and BMS182874 (endothelin-A, ET(A,) receptor antagonist). ET has been shown to affect pharmacological actions of clonidine. The present study was conducted to determine whether alpha(2)-adrenergic and/or I(1)-imidazoline receptors are involved in the augmentation of morphine and oxycodone analgesia by clonidine and BMS182874.

IRL-1620, a tumor selective vasodilator, augments the uptake and efficacy of chemotherapeutic agents in prostate tumor rats.

Background: IRL-1620, a potent endothelin B receptor agonist, enhanced the efficacy of paclitaxel in a breast tumor model, but its effect in prostate cancer is not known. The present study was conducted to evaluate the effect of IRL-1620 on tumor perfusion, uptake of [(14)C]-doxorubicin in the tumor and efficacy of doxorubicin (DOX), and 5-flurouracil (5-FU) in a rat prostate tumor model.

Methods: JHU-4 (Mat-Lu) cells inoculated prostate tumor model in Copenhagen rats was used for the study.

Endothelin ETA receptor blockade potentiates morphine analgesia but does not affect gastrointestinal transit in mice.

Development of analgesic tolerance and constipation remain a major clinical concern during long-term administration of morphine in pain management. Central endothelin mechanisms are involved in morphine analgesia and tolerance. The present study was conducted to investigate the effect of intracerebroventricular (i.

Involvement of central endothelin receptors in neonatal morphine withdrawal.

The involvement of central endothelin (ET) receptors in neonatal morphine tolerance has been demonstrated. The present study investigates the role of central ET receptors in morphine withdrawal in neonatal rats. The aim was to determine whether activation of G-proteins coupled to opioid and ET receptors by morphine and various ET receptor modulators is affected during morphine withdrawal in neonatal rats.

Role of endothelin (ETA) receptors in neonatal morphine withdrawal.

We have previously demonstrated role of central endothelin (ET) receptors in neonatal morphine tolerance. The present study was conducted to investigate involvement of central ET receptors in neonatal rat morphine withdrawal. The aim was to determine activation of G-proteins coupled to opioid and ET receptors by morphine and ET ligands in neonatal rat brains during morphine withdrawal.

Morphine tolerance does not develop in mice treated with endothelin-A receptor antagonists.

Long-term use of morphine leads to development of antinociceptive tolerance. We provide evidence that central endothelin (ET) mechanisms are involved in development of morphine tolerance. In the present study, we investigated the effect of ET(A) receptor antagonists, BQ123 and BMS182874, on morphine antinociception and tolerance in mice.

Role of endothelin in neonatal morphine tolerance.

Management of neonatal opioid tolerance and withdrawal symptoms remains a major challenge in neonatal intensive care units. We provide evidence that central endothelin (ET) mechanisms are involved in the development of morphine tolerance in neonatal rats. Pregnant rats were rendered tolerant to morphine and rat pups were delivered by cesarean section.

A novel combination of opiates and endothelin antagonists to manage pain without any tolerance development.

Several neurotransmitter mechanisms have been proposed as playing a role in the development of morphine tolerance. We provide evidence for the first time that endothelin antagonists can restore morphine analgesia in morphine-tolerant rats and prevent the development of tolerance to morphine. Studies were carried out in rats and mice treated with implanted placebo or implanted morphine pellet.

Central endothelin-B receptor stimulation does not affect morphine analgesia in rats.

Several neurotransmitter mechanisms have been proposed to play a role in the actions of morphine. We reported that centrally administered endothelin A (ETA) receptor antagonists potentiate morphine analgesia in rats. It has also been reported that ETB agonist, IRL1620, has antinociceptive action mediated through opiate receptors in the periphery.

Evidence that morphine tolerance may be regulated by endothelin in the neonatal rat.

Background: Opioids are widely used in the neonatal intensive care units for analgesia and sedation. Management of tolerance and withdrawal symptoms in neonates remains a major challenge.

Objectives: The present study investigates the involvement of a central endothelin (ET) mechanism in the development of tolerance to morphine in neonatal rats.

Endothelin receptor antagonists restore morphine analgesia in morphine tolerant rats.

Several neurotransmitter mechanisms have been proposed to play a role in the development of morphine tolerance. The present study provides evidence for the first time that endothelin (ET) antagonists can restore morphine analgesia in morphine tolerant rats. Tolerance to morphine was induced by subcutaneous implantation of six morphine pellets during a 7-day period.

Potentiation of morphine analgesia by BQ123, an endothelin antagonist.

Several neurotransmitter mechanisms have been proposed to play a role in the actions of morphine. The present study is the first to provide evidence that central endothelin (ET) mechanisms are involved in the modulation of pharmacological actions of morphine. The effect of intracerebroventricular (i.

Activation of signal transduction kinases by tamoxifen.

Purpose: To study the signal transduction mechanisms of tamoxifen via the activation of MAPKs, JNK and ERK in order to understand its regulation of gene expression.

Methods: The effects of tamoxifen (TAM) on the activation of serine/threonine mitogen-activated protein kinase (MAPK, p42/ERK2) and the stress-activated protein kinases (p46 SAPK or c-Jun N-terminal kinase, JNK1) were evaluated using a human cervical epitheloid carcinoma HeLa cell line.

Results: TAM activated both JNK1 and ERK2 activities in a time- and dose-dependent manner in HeLa cells.

Regulation of gene expression of various phase I and phase II drug-metabolizing enzymes by tamoxifen in rat liver.

The objective of the present investigation was to evaluate the effect of tamoxifen (TAM) on the gene expression of different phase I and phase II drug-metabolizing enzymes. Groups of male and female F344/NCr rats were administered either corn oil or TAM (2.8 to 45 mg/kg body wt x 14 days) dissolved in corn oil by gavage.

Transcription regulation of rat glutathione S-transferase Ya subunit gene expression by chemopreventive agents.

Purpose: To study the transcription regulation of rat glutathione S-transferase Ya (rGSTya) subunit gene expression by chemopreventive agents.

Methods: The effects of chemopreventive agents; tamoxifen, genistein, oltipraz, indole-3-carbinol, and various isothiocyanates-sulforaphane, PMITC, PEITC, PBITC, and PPITC, on the transcriptional activation of rGSTya were investigated in cell culture. These were accomplished with a stable human hepatoma Hep G2 cell line transfected with a 1.

Effects of acute and chronic administration of dizocilpine on the pharmacological responses to U-50,488H and brain and spinal cord kappa-opioid receptors in the rat.

In male Sprague-Dawley rats, acute and chronic effects of dizocilpine (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, were determined on the analgesic and hypothermic actions of U-50,488H, a kappa-opioid receptor agonist. In addition, the in vitro effects of MK-801 on the binding of [3H]ethylketocyclazocine ([3H]EKC) to kappa-opioid receptors in brain and spinal cord of the rat were determined. A single injection of MK-801 given 10 min prior to U-50,488H or given twice a day for 4 days dose-dependently enhanced the analgesic action of U-50,488H.

Brain and spinal cord kappa opiate receptors and pharmacological responses to U-50,488H in rats of differing ages.

The analgesic and hypothermic responses to U-50,488H (25 mg/kg IP), a kappa opiate receptor agonist, were determined in male Sprague-Dawley rats aged 4, 8, and 24 weeks. In addition, the characteristics of the binding of [3H]ethylketocylazocine (EKC) to kappa opiate receptors in whole brain and spinal cord of rats of three age groups were also determined. Administration of U-50,488H produced an age-related increase in the analgesic response in the rat, i.

Comparative effects of NG-monomethyl-L-arginine and MK-801 on the abstinence syndrome in morphine-dependent mice.

The effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthase and MK-801, an NMDA receptor antagonist on abrupt and naltrexone-precipitated abstinence symptoms were determined in male Swiss-Webster mice rendered dependent on morphine by subcutaneous implantation of a pellet containing 75 mg of morphine base for 3 days. Mice which served as controls were implanted with placebo pellets. Six hours after pellet removal, mice were injected intraperitoneally with either the vehicle or MK-801 (0.

Methionine-enkephalin concentrations in discrete brain regions, spinal cord, pituitary gland and peripheral tissues of U-50,488H-tolerant and abstinent rats.

Effects were determined of chronic administration and withdrawal of a highly selective kappa-opioid receptor agonist, U-50,488H, on methionine-enkephalin levels in central and peripheral tissues of male Sprague-Dawley rats. Rats were rendered tolerant to and physically dependent on U-50,488H by twice daily injections of 25 mg/kg of this compound for 5 days. Rats deemed abstinent were injected with this drug for 4 days and sacrificed on 5th day.

Effect of morphine tolerance and abstinence on the binding of [3H]naltrexone to discrete brain regions and spinal cord of the rat.

1. The effect of morphine tolerance and abstinence on the binding of [3H]naltrexone to discrete brain regions and spinal cord of the rat was determined. 2.

beta-Endorphin-like immunoreactivity in discrete brain regions, spinal cord, pituitary gland and peripheral tissues of U-50,488H-tolerant and -abstinent rats.

The effect was determined of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzene- acetamide methane sulfonate (U-50,488H), a kappa opioid agonist, -induced tolerance dependence and abstinence on the levels of beta-endorphin in discrete brain regions, spinal cord, pituitary gland, plasma and peripheral tissues of male Sprague-Dawley rats. The brain regions examined were hypothalamus, hippocampus, amygdala, midbrain, corpus striatum, pons-medulla and cortex. The peripheral tissues included kidneys, spleen, adrenals and heart.

Effects of naltrexone pellet implantation on morphine tolerance and physical dependence in the rat.

1. The effect of naltrexone pellets containing either 10 or 30 mg of naltrexone base on the development of tolerance and physical dependence on morphine was assessed in male Sprague-Dawley rats. Tolerance-dependence on morphine was induced by s.

Dizocilpine (MK-801) blocks tolerance to the analgesic but not to the hyperthermic effect of morphine in the rat.

The effect of dizocilpine (MK-801), an N-methyl-D-aspartate receptor antagonist, on the development of tolerance to the analgesic and hyperthermic effects of morphine was determined in the rat. Tolerance to morphine in male Sprague-Dawley rats was induced by implanting subcutaneously 6 morphine pellets during a 7-day period. Two schedules of intraperitoneal injections of MK-801 were used.