Cisplatin increases brain 2-arachidonoylglycerol (2-AG) and concomitantly reduces intestinal 2-AG and anandamide levels in the least shrew

Darmani, Nissar A.; McClanahan, Bryan; Trinh, Chung; Petrosino, Stefania; Valenti, Marta; Marzo, Vincenzo Di

doi:10.1016/j.neuropharm.2005.04.007

Cited by 42 publications

(53 citation statements)

References 61 publications

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“…According to the current results, there is an enhancement of AEA affinity/potency in the presence of LXA 4 , which could help bring AEA back to the status of a "true" endocannabinoid, potentially reducing the efficacy of 2-AG effects. Thus, our data strongly suggest the existence of a functional selectivity between AEA and 2-AG, which is in good agreement with recent data proposing that these two molecules may mediate substantially distinct physiological effects and regulate each other (37)(38)(39). We found that FSK-stimulated cAMP production is more strongly and more efficiently suppressed by the costimulation with AEA and LXA 4 compared with AEA alone.…”

Section: Resultssupporting

confidence: 93%

Anti-inflammatory lipoxin A ₄ is an endogenous allosteric enhancer of CB ₁ cannabinoid receptor

Pamplona

Ferreira

Lima

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

162

198

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Allosteric modulation of G-protein–coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A 4 is an endogenous allosteric enhancer of the CB 1 cannabinoid receptor. Lipoxin A 4 was detected in brain tissues, did not compete for the orthosteric binding site of the CB 1 receptor (vs. 3 H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating the effects of this endocannabinoid both in vitro and in vivo. In addition, lipoxin A 4 displayed a CB 1 receptor-dependent protective effect against β-amyloid (1–40)-induced spatial memory impairment in mice. The discovery of lipoxins as a class of endogenous allosteric modulators of CB 1 receptors may foster the therapeutic exploitation of the endocannabinoid system, in particular for the treatment of neurodegenerative disorders.

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Section: Resultssupporting

confidence: 93%

Anti-inflammatory lipoxin A ₄ is an endogenous allosteric enhancer of CB ₁ cannabinoid receptor

Pamplona

Ferreira

Lima

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

162

198

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“…Recently Darmani et al (2005) showed that very high doses of URB597 (5-10 mg/kg) administered 10 min before 2-AG or cisplatin did not prevent emesis in the least shrew. However, in the present experiment, when much lower doses of URB597 were administered 2 h before LiCl (e.g., Fegley et al 2005), URB597 facilitated the effect of anandamide in suppressing nausea in rats as measured by suppressed conditioned rejection reactions and enhanced conditioned ingestion reactions in rats.…”

Section: Discussionmentioning

confidence: 99%

“…Future studies will evaluate the potential of URB597 administered 2 h before cisplatin to modify emesis in the Suncus murinus (house musk shrew). Furthermore, it is known that the efficacy of various emetic stimuli can be species dependent (see Darmani et al 2005). Nevertheless, it has been shown previously that URB597 can magnify the hypothermic response produced by anandamide (Fegley et al 2005) and produce anxiolytic-like responses in both the zero-maze test and the isolation-induced ultrasonic emission test when administered 2 h before the behavioral test (Kathuria et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat

et al. 2006

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Rationale The endogenous cannabinoid system plays a vital role in the control of nausea and emesis. Because of the rapid breakdown and hydrolysis of endocannabinoids, such as anandamide, the therapeutic effects may be enhanced by prolonging their duration of action. Objective The present experiment evaluated the potential of various doses of URB597, a fatty acid amide hydrolase (FAAH) inhibitor, alone and in combination with systemic administration of anandamide to modulate the establishment of lithium-induced conditioned taste reactivity responses in rats. Materials and methods In experiment 1, on the conditioning day, rats first received an injection of 0.3 mg/kg URB597, 0.15 mg/kg URB597, or vehicle and then received a second injection of anandamide (5 mg/kg) or vehicle, before a 3-min exposure of 0.1% saccharin by intraoral infusion. Immediately after the saccharin exposure, the rats were injected with lithium chloride. On each of three test days, rats received a 3-min intraoral infusion of saccharin solution, and the taste reactivity responses were videotaped and monitored. In experiment 2, the effects of pretreatment with the CB 1 antagonist, AM-251, on URB597 and anandamide-induced suppressed aversion was evaluated.Results Administration of URB597 alone and in combination with anandamide reduced active rejection reactions elicited by a LiCl-paired saccharin solution; both effects were reversed by pretreatment with AM-251, suggesting that they were CB 1 receptor mediated. Conclusions The results suggest that prolonging the action of anandamide by pretreatment with the FAAH inhibitor, URB597, suppresses lithium-induced nausea in the rat.

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“…Depending on the model used and the dose of chemotherapeutic, the first phase occurs from 1-2 hours, up to one day, post-administration (acute-phase). The second phase follows an emesis-free period of one to several days, when a second series of bouts of emesis (delayed-phase) occurs [5,10,14,23]. Antagonism of 5-HT3R's is effective against acute-phase, but is only minimally effective or ineffective against delayedphase emesis [1,5,27].…”

Section: Introductionmentioning

confidence: 99%

“…The anatomical and neurochemical substrates of delayed-phase emesis have yet to be elucidated, although recent work points towards NK-1 neurokinin receptor activation by Substance P [5,12,46,48] and/or 5-HT4R activation by 5-HT [36]. In addition, significant evidence has been collected for both pro-emetic [14,27] and anti-emetic roles [2,12,13,27,44,50,51] for cannabinoid-related activity.…”

Section: Introductionmentioning

confidence: 99%

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Ray

Darmani

2007

Brain Research

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Chemotherapy is an effective treatment but difficult to tolerate due to side effects like vomiting. Studies on the etiology of chemotherapy-related emesis have implicated brainstem nuclei and the neurotransmitter Substance P, among other substrates. Since rodents do not vomit, other species have been necessary as alternative models of chemotherapy-induced emesis. Of these, the least shrew (Cryptotis parva) has proven valuable due to its small size, hardiness, and close phylogenetic relationship with primates. However, very little neuroanatomical data on C. parva exist. We used histological and immunohistochemical techniques to provide neuroanatomical data to help validate C. parva as a model organism, especially for emesis research. Brains were sectioned and stained for Nissl substance or myelin, or immunofluorescently labeled for Substance P. Sections were photographed, traced, and reconstructed with standardized zero points, and these data used to create a stereotaxic atlas. The brain of C. parva was similar to but smaller than other mammalian brains, with the cerebellum and hippocampus demonstrating the biggest differences. Differences appeared to be related to the small size of the brain and the metabolic compromises required of such a small mammal. Substance P-like immunoreactivity (SPL-IR) was semiquantitatively mapped, and correlated very well with SPL-IR observed in other species. Dense SPL-IR areas included the periaqueductal grey, trigeminal nuclei, dorsal raphe, and emesis-related brainstem nuclei including the area postrema and solitary tract nucleus. These data demonstrate that the anatomical differences between C. parva and other mammals will not preclude its use as a model organism.

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Cisplatin increases brain 2-arachidonoylglycerol (2-AG) and concomitantly reduces intestinal 2-AG and anandamide levels in the least shrew

Cited by 42 publications

References 61 publications

Anti-inflammatory lipoxin A ₄ is an endogenous allosteric enhancer of CB ₁ cannabinoid receptor

Anti-inflammatory lipoxin A ₄ is an endogenous allosteric enhancer of CB ₁ cannabinoid receptor

Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

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Cisplatin increases brain 2-arachidonoylglycerol (2-AG) and concomitantly reduces intestinal 2-AG and anandamide levels in the least shrew

Cited by 42 publications

References 61 publications

Anti-inflammatory lipoxin A 4 is an endogenous allosteric enhancer of CB 1 cannabinoid receptor

Anti-inflammatory lipoxin A 4 is an endogenous allosteric enhancer of CB 1 cannabinoid receptor

Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

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Anti-inflammatory lipoxin A ₄ is an endogenous allosteric enhancer of CB ₁ cannabinoid receptor

Anti-inflammatory lipoxin A ₄ is an endogenous allosteric enhancer of CB ₁ cannabinoid receptor