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Chronic treatment with the cannabinoid 1 antagonist rimonabant altered vasoactive cyclo-oxygenase-derived products on arteries from obese Zucker rats.
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To investigate the effect of chronic cannabinoid 1 antagonism on vascular prostanoid production, obese Zucker rats were treated with rimonabant (10 mg/kg per day) during 20 weeks and then vascular and endothelial reactivity were assessed in aortic rings by analyzing response to phenylephrine and
Treatment with a heme oxygenase 1 inducer enhances the antinociceptive effects of µ-opioid, δ-opioid, and cannabinoid 2 receptors during inflammatory pain.
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The administration of µ-opioid receptor (MOR), δ-opioid receptor (DOR), and cannabinoid 2 receptor (CB2R) agonists attenuates inflammatory pain. We investigated whether treatment with the heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), could modulate the local effects and
A cytochrome P450 isozyme having aldehyde oxygenase activity plays a major role in metabolizing cannabinoids by mouse hepatic microsomes.
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A cytochrome P450 (designated P450 MUT-2) which catalyses the oxidation of 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC) to delta 8-THC-11-oic acid has been purified from hepatic microsomes of untreated male mice. Analysis of NH2-terminal sequence suggests that the isozyme is a member of
Functional relevance of the cannabinoid receptor 2 - heme oxygenase pathway: a novel target for the attenuation of portal hypertension.
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OBJECTIVE
In liver cirrhosis, inflammation triggers portal hypertension. Kupffer cells (KC) produce vasoconstrictors upon activation by bacterial constituents. Here, we hypothesize that the anti-inflammatory action of the cannabinoid receptor 2 (CB2) agonists JWH-133 and GP 1a attenuate portal
The role of carbon monoxide, heme oxygenase 1, and the Nrf2 transcription factor in the modulation of chronic pain and their interactions with opioids and cannabinoids
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Chronic pain and its associated comorbidities are difficult to treat, even when the most potent analgesic compounds are used. Thus, research on new strategies to effectively relieve nociceptive and/or emotional disorders accompanying chronic pain is essential. Several studies have demonstrated the
Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with biliary cirrhosis.
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Recent studies have shown that the activated endocannabinoid system participates in the increase in IHR (intrahepatic resistance) in cirrhosis. The increased hepatic production of vasoconstrictive eicosanoids is involved in the effect of endocannabinoids on the hepatic microcirculation in cirrhosis;
Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content.
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1. The oral sedative potencies of cannabis herb, crude ethanolic and petroleum-ether fractions, were assayed against delta'-trans-tetrahydrocannabinol (THC) administered orally to mice, by measuring spontaneous motor activity over 30 min periods, at selected times, up to 6 h. 2. The THC contents of
Effects of repeated administration with CP-55,940, a cannabinoid CB1 receptor agonist on the metabolism of the hepatic heme.
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Drugs metabolised by cytochrome P450 (CYP) such as analgesics may induce acute attacks in patients with hepatic porphyrias. In recent years, preclinical and clinical studies have suggested that cannabinoid pharmaceutical preparations may be potentially useful in the treatment of pain. The purpose of
Inhibition of the production of endothelium-derived hyperpolarizing factor by cannabinoid receptor agonists.
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1. The endogenous cannabinoid, anandamide, has been reported to induce an 'endothelium-derived hyperpolarizing factor (EDHF)-like' relaxation in vitro. We therefore investigated the effects of cannabinoid CB1 receptor agonists; HU 210, delta9-tetrahydrocannabinol (delta9-THC) and anandamide, and a
Cannabinoid CB1 receptor and endothelium-dependent hyperpolarization in guinea-pig carotid, rat mesenteric and porcine coronary arteries.
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1. The purpose of these experiments was to determine whether or not the endothelium-dependent hyperpolarizations of the vascular smooth muscle cells (observed in the presence of inhibitors of nitric oxide synthase and cyclo-oxygenase) can be attributed to the production of an endogenous cannabinoid.
Recent advances in the metabolism of cannabinoids.
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This review describes recent advances in the metabolism of cannabinoids. Cannabidiol was metabolized to cannabielsoin, 6 beta-hydroxymethyl-delta 9-tetrahydrocannabinol and an oxepine derivative through epoxide intermediates by hepatic microsomal enzymes containing cytochrome P450 of animals.
Effects of two cannabinoids on hepatic microsomal cytochrome P-450.
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The effects of cannabidiol (CBD) and delta 9-tetrahydrocannabinol (delta 9-THC) on the synthesis and degradation of hepatic microsomal cytochrome P-450 were studied in mice. Cannabinoids used (10, 50 and 100 mg/kg, i.p.) did not affect delta-aminolevulinic acid synthetase activity in the liver.
Cannabinoid CB1 receptors mediate the effects of dipyrone.
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Dipyrone is a non-steroidal anti-inflammatory drug used primarily as an analgesic and antipyretic. Some hypothesize that dipyrone activity can modulate other pathways, including endocannabinoid signalling. Thus, the aim of the present study was to evaluate the possible role of endocannabinoids in
Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman.
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The hepatic microsomal metabolism of cannabinoids was studied using the liver from an old woman. delta 8-Tetrahydrocannabinol, delta 9-tetrahydrocannabinol and cannabinol were biotransformed to their respective 11-hydroxy metabolites by a microsomal fraction with specific activities (pmol/min/mg
The role of carbon monoxide on the anti-nociceptive effects and expression of cannabinoid 2 receptors during painful diabetic neuropathy in mice.
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The activation of cannabinoid 2 receptors (CB2R) attenuates chronic pain, but the role played by carbon monoxide synthesized by the inducible heme oxygenase 1 (HO-1) on the anti-nociceptive effects produced by a selective CB2R agonist, JWH-015, during painful diabetic neuropathy remains unknown.
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