Papel del sistema cannabinoide endógeno en el intestino / Role of the endogenous cannabinoid system in the gut / Papel do sistema canabinoide endógeno no intestino

RESUMEN El sistema cannabinoide endógeno es un nuevo sistema de comunicación intercelular que constituye una pieza crucial en la regulación de la función intestinal. Se realizó una revisión bibliográfica con el objetivo de describir cómo el sistema cannabinoide endógeno modula la función intestinal. Se consultaron un total de 31 referencias bibliográficas entre libros, revistas, tesis doctorales y artículos en internet. Se encontró que los endocannabinoides son inmunomoduladores a nivel intestinal, que el sistema cannabinoide endógeno regula la composición de la microbiota intestinal y esta a su vez determina la concentración de los endocannabinoides, además tanto la secreción como la motilidad intestinal disminuyen por estimulación del sistema cannabinoide endógeno. Los receptores de cannabinoides, los endocannabinoides anandamida y 2-araquidonoilglirerol y las proteínas responsables de su síntesis y degradación están ampliamente distribuidos en el intestino en condiciones fisiológicas, aumentando su expresión en la enfermedad inflamatoria intestinal lo que le permite regular la función intestinal en ambas condiciones. El sistema cannabinoide endógeno tiene un enorme potencial terapéutico en la enfermedad inflamatoria intestinal debido a los efectos inmunosupresores, antiinflamatorios y analgésicos que posee.

ABSTRACT The endogenous cannabinoid system is a new intercellular communication system that constitutes a crucial piece in the regulation of intestinal function. A bibliographic review was carried out in order to describe how the endogenous cannabinoid system modulates intestinal function. A total of 31 bibliographic references were consulted between books, magazines, doctoral theses and articles on the internet. It was found that endocannabinoids are immunomodulatory at the intestinal level, that the endogenous cannabinoid system regulates the composition of the intestinal microbiota and this in turn determines the concentration of endocannabinoids, in addition both secretion and intestinal motility decrease by stimulation of the endogenous cannabinoid system. The cannabinoid receptors, the endocannabinoids anandamide and 2-arachidonoylglirerol, and the proteins responsible for their synthesis and degradation are widely distributed in the intestine under physiological conditions, increasing their expression in inflammatory bowel disease, which allows it to regulate intestinal function in both conditions. The endogenous cannabinoid system has enormous therapeutic potential in inflammatory bowel disease due to its immunosuppressive, anti-inflammatory and analgesic effects.

RESUMO O sistema canabinoide endógeno é umnovo sistema de comunicação intercelular que constitui uma peça crucial na regulação da função intestinal. Foi realizada uma revisão bibliográfica para descrever como o sistema canabinoide endógeno modula a função intestinal. Foram consultadas 31referências bibliográficas entre livros, revistas, teses de doutorado e artigosna internet. Verificou-se que os endocanabinoides são imunomoduladores em nível intestinal, que o sistema canabinoide endógeno regula a composição da microbiota intestinal e esta, por sua vez, determina a concentração de endocanabinoides, além da diminuição da secreção e da motilidade intestinal pela estimulação do sistema canabinoide endógeno. Os receptores canabinoides, os endocanabinoides anandamida e 2-araquidonoilglirerol e as proteínas responsáveis ​​por sua síntese e degradação estão amplamente distribuídos no intestino em condições fisiológicas, aumentando sua expressão em doenças inflamatórias intestinais que permitem regular a função intestinal em ambas as condições. O sistema canabinoide endógeno apresenta enorme potencial terapêutico na doença inflamatória intestinal devido aos seus efeitos imunossupressores, antiinflamatórios e analgésicos.

Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

An integrative overview of the cannabinergic system and mental health / Una revisión exhaustiva del sistema cannabinérgico y la salud mental

Abstract Background The endocannabinoid system (eCBs) is one of the modulatory systems widely expressed in the brain. It consists of receptors expressed in the cytoplasmic (CB1 and CB2), the mitochondrial membrane (CB1), and the endogenous ligands known as endocannabinoids, such as anandamide, 2AG and oleamide. CB1 has been found in excitatory and inhibitory neurons in the pre- and post-synaptic membranes. It is expressed in several brain areas such as the hippocampus, dorsal, and ventral striatum, amygdala and prefrontal cortex. The eCBs has been involved in the regulation of learning and memory, mood, energy balance, sleep, and drug addiction. Objective Integrate existing information about the eCBs and its role in brain function and mental health. Method Review of the information of basic and clinical relevance obtained from indexed scientific journals (PubMed/Medline, Scopus). Results Basic and clinical research on eCBs related to central nervous system function is described. Discussion and conclusion At present, the study of eCBs is of importance. The development of drugs that affect this system may be clinically useful to control different debilitating diseases. This is an area of interest to the scientific community and health care providers.

Resumen Antecedentes El sistema de endocannabinoides (eCBs) es uno de los sistemas moduladores más ampliamente expresados en el cerebro. Se compone de receptores expresados en la membrana citoplasmática (CB1 y CB2) y en la membrana mitocondrial (CB1) y ligandos endógenos conocidos como endocannabinoides, como anandamida, 2AG y oleamida. El CB1 se ha encontrado en neuronas excitadoras e inhibidoras, en las membranas pre- y pos-sináptica, en varias áreas cerebrales como el hipocampo, el estriado dorsal y ventral, y en la amígdala y la corteza prefrontal. El eCBs se ha relacionado con la regulación del aprendizaje y la memoria, del estado afectivo, del equilibrio energético, del sueño y del proceso de la adicción a las drogas. Objetivo Integrar la información existente sobre el eCBs y su función sobre los procesos cerebrales y la salud mental. Método Revisión de la información de relevancia básica y clínica obtenida de revistas científicas indexadas (PubMed/Medline, Scopus). Resultados Se describe de manera concisa información de interés básico y clínico de la investigación sobre el eCBs relacionada con la función del sistema nervioso central. Discusión y conclusión En la actualidad, el estudio del eCBs es indispensable debido a su potencial terapéutico. El desarrollo de fármacos que afecten este sistema puede ser clínicamente útil para controlar diferentes enfermedades debilitantes. Ésta es un área de interés para la comunidad científica y los proveedores de salud.

Research progress in role and mechanism of endogenous cannabinoid system in hepatic disease / 中国药学杂志

OBJECTIVE: To analyze recent studies on the role of the endocannabinoid system in liver disease and related mechanism. METHODS: Reading domestic and international documents in recent years, we concluded a comprehensive integrated about them. RESULTS: This paper reviews the important role of the endocannabinoid in the development of liver disease, which focuses on the prevention and protection of the endocannabinoid on viral hepatitis, alcoholic fatty liver disease, non-alcoholic fatty liver disease, cholestatic liver disease and liver ischemia-reperfusion injury and the development of hepatic fibrosis and hepatic encephalopathy. CONCLUSION: Endocannabinoid system plays an important role in the treatment of liver disease. But for its complex mechanism of action, we need further research.

Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E2 (PGE2, 2 μg/paw) in the rat’s hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE2, which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 μg/paw) and AM-630 (100 μg/paw) were used as CB1 and CB2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 μg dipyrone (mean = 5.825 ± 2.842 g), 20 μg diclofenac (mean = 4.825 ± 3.850 g) and 40 μg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac and indomethacin.

Cannabinoid system and its role in the intestinal motility regulation / 国际外科学杂志

Cannabinoids have been used in clinic for many years.However,their effective mechanisms,especially the role of the endogenous cannabinoid system in the regulation of intestinal motility are still poorly understood.In this article,we introduced that the compositions of the Cannabinoid family members,including their receptors,analogues,and antagonists,and the effects of them on the gastrointestinal movement.We provide the useful update information for the further clinic and experiment study on the cannabinoid family and the endocannabinoid system.