“The function of the endocannabinoid system (ECS) in the renal tissue is not completely understood.
We studied the effect of compounds modulating the activity of cannabinoid CB receptors on the active reabsorption of Na+ in LLC-PK1 cells.
Tag Archives: Cannabinoids
The endocannabinoid system in renal cell: Regulation of Na+ transport by CB1 receptors through distinct cell signaling pathways.
“The function of the endocannabinoid system (ECS) in the renal tissue is not completely understood. Kidney function is closely related to ion reabsorption in the proximal tubule, the nephron segment responsible for the reabsorption of 70- 80% of the filtrate.
We studied the effect of compounds modulating the activity of cannabinoid CB receptors on the active reabsorption of Na+ in LLC-PK1 cells.
CONCLUSION AND IMPLICATIONS:
ECS is expressed in LLC-PK1 cells. Both CB1 and TRPV1 regulate (Na+ +K+ )-ATPase activity in these cells, and are modulated by lipid and peptide CB1 ligands, which act via different signaling pathways.”
Enhanced vasorelaxation effect of endogenous anandamide on thoracic aorta in renal vascular hypertension rats.
“Emerging evidence indicated that anandamide (AEA) stimulated vasorelaxation in both spontaneously hypertensive rats (SHRs) and L-NAME-induced hypertensive rats. Yet it remains unknown whether AEA modulates vasomotion of aorta in renovascular hypertensive (RVH) rats.
The aim of present study was to explore the effect of AEA on relaxation of thoracic aortas in two-kidney one-clip (2K1C)-induced RVH rats.
Taken together, the present study demonstrated that AEA enhanced endothelium-dependent aortic relaxation through activation of both CB1 and CB2 receptors and P-eNOS/NO pathway in 2K1C rats.”
A synergistic interaction of 17-β-estradiol with specific cannabinoid receptor type 2 antagonist/inverse agonist on proliferation activity in primary human osteoblasts.
“The bone remodeling process is influenced by various factors, including estrogens and transmitters of the endocannabinoid system. In osteoblasts, cannabinoid receptors 2 (CB-2) are expressed at a much higher level compared to CB-1 receptors. Previous studies have shown that estrogens could influence CB-2 receptor expression.
In the present study, the possible interactions of a specific CB-2 agonist and a specific CB-2 antagonist/inverse agonist with 17-β-estradiol were investigated in primary human osteoblasts (HOB)…
In conclusion, for the first time a synergistic interaction between 17-β-estradiol and specific CB-2 antagonist/inverse agonist was observed in HOB.
Understanding the molecular pathways of this interaction would be of great importance in developing more efficient and safer drugs for treating or preventing bone diseases.”
[Changes over time of cannabinoid receptor 1 in hippocampus of status epilepticus rats].
To explore the changes over time of cannabinoid receptor 1 (CB1R) in hippocampus of status epilepticus (SE) rats…
There is a protective increase of CB1R in hippocampus of SE rats and then it returns to normal.
Thus CB1R may he involved in the occurrences and terminations of seizures.”
Selective Reduction of THC’s Unwanted Effects through Serotonin Receptor Inhibition
“While recreational marijuana users may seek the full range of its effects, broad medical use of THC—including for pain, nausea, and anxiety—is hindered by them.
In a new study, Xavier Viñals, Estefania Moreno, Peter McCormick, Rafael Maldonado, Patricia Robledo, and colleagues demonstrate that the cognitive effects of THC are triggered by a pathway separate from some of its other effects.
That pathway involves both a cannabinoid receptor and a serotonin receptor, and when this pathway is blocked, THC can still exert several beneficial effects, including analgesia, while avoiding impairment of memory.
The results of this study are potentially highly important, in that they identify a way to reduce some of what are usually thought of as THC’s unwanted side effects when used for medicinal purposes while maintaining several important benefits, including pain relief.
The widening acceptance of a role for THC in medicine may be accelerated by the option to reduce those side effects by selective pharmacological disruption or blocking of the heteromer.”
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002193
Anandamide exerts its antiproliferative actions on cholangiocarcinoma by activation of the GPR55 receptor
“We have previously shown that AEA exerts growth-suppressing effects on cholangiocarcinoma by inducing apoptosis.
At the time, we assumed that AEA was acting via a receptor-independent mechanism.
However, given the recent discovery and characterization of GPR55 as a novel AEA receptor, our data need to be reassessed to determine if GPR55 activation can decrease cholangiocarcinoma cell proliferation.
Thus, our aims are to determine if these AEA-mediated effects on cholangiocarcinoma cell growth can be attributed to the activation of GPR55.
This data represent the first evidence that GPR55 activation by anandamide can lead to the recruitment and activation of the Fas death receptor complex and that targeting GPR55 activation may be a viable option for the development of therapeutic strategies to treat cholangiocarcinoma.
In conclusion, we have clearly demonstrated a role for GPR55 in the antiproliferative effects of AEA in vivo andin vitro…
Cholangiocarcinoma has a very poor prognosis and survival rate; therefore we propose that the development of novel therapeutic strategies that target GPR55 may prove beneficial for the treatment of this devastating disease.
Consistent with our observation that AEA has antiproliferative and pro-apoptotic properties, cannabinoids of various origins (endogenous, plant-derived or synthetic analogues) have been shown to suppress cancer cell growth in vitro as well as in vivo.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126905/
The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway.
“Cholangiocarcinomas are cancers that have poor prognosis and limited treatment options.
Marijuana and its derivatives have been used in medicine for many centuries.
…cannabinoids might be effective antitumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture and in laboratory animals.
Indeed, we have recently demonstrated that the endocannabinoid anandamide (AEA) has antiproliferative effects on cholangiocarcinoma cell lines in vitro via a cannabinoid receptor-independent pathway involving the stabilization of lipid raft-membrane structures and the recruitment of death-receptor complexes into the lipid rafts.
Modulation of the endocannabinoid system may be important in cholangiocarcinoma treatment.
The antiproliferative actions of the noncanonical Wnt signaling pathway warrants further investigation to dissect the mechanism by which this may occur.
We propose that the development of novel therapeutic strategies aimed at modulating the endocannabinoid system, or mimicking the mode of action of AEA, would prove beneficial for the treatment of this devastating disease.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2604798/
Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling
“Cholangiocarcinomas are devastating cancers of intrahepatic and extrahepatic origin that are increasing in both their worldwide incidence and mortality rates.
Conventional chemotherapy and radiation therapy are not effective in prolonging long-term survival; therefore it is important to understand the cellular mechanisms of cholangiocarcinoma cell growth with a view to develop novel chemopreventive strategies.
We have recently demonstrated that the endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) exert opposing effects on cholangiocarcinoma cell growth in vitro via cannabinoid receptor-independent mechanisms.
AEA increased presenilin 1 expression and recruitment into the γ-secretase complex whereas 2-AG increased expression and recruitment of presenilin 2.
The development of novel therapeutic strategies aimed at modulating the endocannabinoid system, or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.
We propose that the development of novel therapeutic strategies aimed at modulating the endocannabinoid system, or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for the treatment of this devastating disease.”
Opposing actions of endocannabinoids on cholangiocarcinoma growth: recruitment of Fas and Fas ligand to lipid rafts.
“Cholangiocarcinomas are devastating cancers of biliary origin with limited treatment options…
Marijuana and its derivatives have been used in medicine for many centuries, and presently there is an emerging renaissance in the study of the therapeutic effects of cannabinoids…
In addition, cannabinoids might be effective antitumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture and in laboratory animals.
Modulation of the endocannabinoid system is being targeted to develop possible therapeutic strategies for a number of cancers; therefore, we evaluated the effects of the two major endocannabinoids, anandamide and 2-arachidonylglycerol, on numerous cholangiocarcinoma cell lines…
These findings suggest that modulation of the endocannabinoid system may be a target for the development of possible therapeutic strategies for the treatment of this devastating cancer.
Consistent with our observation that AEA has antiproliferative and proapoptotic properties, cannabinoids of various origins (endogenous, plant-derived, or synthetic analogues) have been shown to suppress cancer cell growth in vitro as well as in vivo.
In conclusion, we have clearly demonstrated opposing actions of the endocannabinoids AEA and 2-AG on cholangiocarcinoma cell proliferation and have shown that these actions are via a cannabinoid receptor-independent but lipid raft-mediated pathway. Furthermore we have shown that the antiproliferative/proapoptotic actions of AEA are mediated via an accumulation of ceramide and the recruitment of the Fas death receptor into the lipid rafts. Cholangiocarcinoma has a very poor prognosis and survival rate; therefore we propose that the development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA would prove beneficial for the treatment of this devastating disease.”