Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Apr 2009
Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.
1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. ⋯ The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.
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Clin. Exp. Pharmacol. Physiol. · Mar 2009
Cardioprotective effects of granulocyte colony-stimulating factor in angiotensin II-induced cardiac remodelling.
1. Granulocyte colony stimulating factor (G-CSF) is reported to have a beneficial effect on cardiac dysfunction in postinfarction and doxorubicin-induced cardiomyopathy. Thus, the aim of the present study was to investigate the effects of G-CSF on cardiac remodelling in angiotensin (Ang) II-induced hypertrophy. 2. ⋯ These results suggest that G-CSF reduces AngII-induced hypertrophy. Modulation of the expression of the ACE isoforms contributes to regression of AngII-induced cardiac hypertrophy. The effect of G-CSF to prevent cardiac fibrosis and hypertrophy may be mediated, in part, via inhibition of OPN expression and p70S6 kinase phosphorylation.
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Clin. Exp. Pharmacol. Physiol. · Jan 2009
Antinociception versus serum concentration relationships following acute administration of intravenous morphine in male and female Sprague-Dawley rats: differences between the tail flick and hot plate nociceptive tests.
1. Antinociception versus serum morphine concentration relationships were defined in male and female Sprague-Dawley rats administered single intravenous (i.v.) bolus doses of morphine, using the hot plate (2.1-14 mg/kg) and tail flick tests (1-8 mg/kg). 2. Serum concentrations of morphine and morphine-3-glucuronide (M3G), its major metabolite in the rat, were assayed using high-performance liquid chromatography (HPLC) with electrochemical detection. 3. ⋯ Morphine ED(50) and EC(50) values (95% confidence intervals) for antinociception in the hot plate test were significantly lower (P < 0.05) in male rats (ED(50) 8.4 mg/kg (7.6-9.2); EC(50) 1.8 nmol/L (1.5-2.1)) compared with female rats (ED(50) 10.6 mg/kg (9.1-12.0); EC(50) 3.7 nmol/L (3.4-4.1)). However, in the tail flick test, there was no significant difference between male and female rats in ED(50) (1.8 (0.4-3.3) and 1.4 mg/kg (0.4-2.5), respectively) or EC(50) (0.5 (0.3-0.6) and 0.4 nmol/L (0.2-0.5), respectively) values. 6. Supraspinal attenuation of morphine antinociception by M3G may account for these differences.
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Clin. Exp. Pharmacol. Physiol. · Nov 2008
ReviewSuppressing NADPH oxidase-dependent oxidative stress in the vasculature with nitric oxide donors.
1. Reactive oxygen species produced in the vasculature, including superoxide anion, contribute to the pathogenesis of cardiovascular disease states, such as atherosclerosis. A critical source of superoxide is vascular NADPH oxidase and upregulation of this enzyme brings about the oxidative stress underlying atherosclerosis. ⋯ These problems of nitrates have not only limited their therapeutic exploitation, but have also stifled interest in newer-generation NO donors. 3. Recent evidence indicates that, in stark contrast with the organic nitrates, the newer-age diazeniumdiolate NONOate class of NO donors suppress vascular NADPH oxidase-dependent superoxide production and are less likely to induce tolerance, making them more suitable for suppression of oxidative stress in atherosclerosis. 4. Here, it is hypothesized that NONOates provide a novel means of suppressing NADPH oxidase-dependent oxidative stress to restore vascular NO levels to prevent, and even reverse, atherosclerosis.
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Clin. Exp. Pharmacol. Physiol. · Nov 2008
Comparative StudySpinal mu-opioid receptor expression and hyperalgesia with dexamethasone in chronic adjuvant-induced arthritis in rats.
1. It is known that inflammation influences peripheral and central mu-opioid receptor expression. Previous studies have indicated that glucocorticoids may influence the density of mu-opioid receptors. ⋯ The AA + dexamethasone group showed a significant decrease in hyperalgesia on Day 6 compared with the AA group, but hyperalgesia increased significantly on Day 21 in the AA + dexamethasone group compared with the AA group. 4. The effects of long-term dexamethasone on both spinal mu-opioid receptor expression and hyperalgesia during persistent AA inflammation are time dependent. In addition, the effect of long-term dexamethasone administration on hyperalgesia during persistent arthritis inflammation needs to be investigated further.