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Scientists find a new pharmacological target to modulate the effect of cannabinoids through their CB1 receptors

The scientific team at the Faculty of Biology of the UB.

The scientific team at the Faculty of Biology of the UB.

CB1-CB2 receptor heteromers in rat brain.

CB1-CB2 receptor heteromers in rat brain.

05/07/2012

A group or researchers from the University of Barcelona and the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), a centre for biomedical network research on neurodegenerative diseases dependant on the Ministry of Economics and Competitiveness through the Carlos III Health Institute, has shown, in a research published in the Journal of Biological Chemistry, the expression of complexes known as heteromerswithin the cannabinoid receptors CB2 and CB1. The results of this research may help in the better understanding of alterations where the CB1 receptor participates, such as in chronic pain, Parkinson's disease, cerebral trauma or brain tumours in which there may be a high inflammatory component.  

 

Cannabis, commonly known as marihuana, is one of the most widely abused drugs among the European population. Its psychoactive substances act by interacting with proteins from the membrane of the cells which are their CB1 and CB2 receptors. In a natural way and independent of the marihuana, the cells themselves release compounds which are called endocannabinoids and they activate the CB1 and CB2 receptors to produce a physiological response.

 
The CB1 cannabinoid receptor is one of the most abundant receptors in the brain and it helps to regulate movement, as well as functioning as a therapeutic target for the treatment of pain, inflammation and Parkinson's disease, and it alleviates some side effects in cancer patients. Nevertheless, the CB2 cannabinoid receptors are far from being abundant in the brain and their function is not completely clear. This makes these receptors a subject of scientific interest, precisely because of the scarcity of information regarding their functioning.
 
The existence and function of the CB2 receptors in the neurons has always been controversial. This new research now offers two relevant conclusions: in the first place, the expression of CB2 as a protein in the neurons is confirmed and, in the second place, it is shown that the CB2 receptors may be a new pharmacological target for the modulation of the effect of cannabinoids through the CB1 receptor, forming CB1-CB2 heteromers which are expressed in the brain. The mission of CB2 in these heteromers is to repress the CB1 receptors, which could explain that during processes of inflammation, the CB2 receptors act as a brake on the CB1 receptors. The research shows that it is necessary to take these heteromers into account for the effective design of medicines to counteract cannabinoid receptors, since these heteromers are the real targets and they show properties that are different from the individual receptors.
 
This project has been carried out by the Molecular Neurobiology Research Group from the University of Barcelona, integrated in the campus of international excellence Barcelona Knowledge Campus (BKC), and the following lecturers worked on it: Dr. Peter McCormick, Dr. Enric I. Canela, Dr. Antoni Cortés, Dr. Carme Lluís, Dr. Josefa Mallol, Dr. Vicent Casadó, Dr. David Moreno-Delgado and Dr. Estefanía Moreno and the doctoral student Lucía Callén. Also participating in the project were Dr. José Luis Lanciego and Dr. Rafael Franco from the University of Navarra.
 
Parkinson's disease affects around 70,000 people in Spain
 
Neurodegenerative diseases (NDD) represent one of the most important health challenges in developed countries, because of their consequences for health and quality of life of those who suffer from them, as well as the socioeconomic burden that they represent. They are generally chronic, for the moment incurable, diseases and their common denominator is the death of neurons in different regions of the nervous system, which leads to the functional deterioration of the affected parts.
 
In the case of Parkinson's disease, there are 70,000 people affected in Spain and the disease is characterized principally by the loss of neurons and the formation of Lewy bodies and Lewy neurites in the black substance and the consequent loss of striatal dopamine (DA). Nevertheless, it is currently well known that Parkinson's disease is a multisystemic neurodegenerative process, in which, as the neurodegenerative process evolves, numerous regions of the nervous system are affected and there exists a deficit in various systems of neurotransmission and neuromodulation.
  
The Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) is one of the reference centres in Spain for research on neurodegenerative diseases (NDD), such as Alzheimer’s, Parkinson’s, Huntington’s diseases and other ataxias and neuromuscular diseases. It was created in 2006 and its main objective is to promote basic biomedical, clinical and epidemiological research, as well as to ensure that the research carried out in laboratories can be put into practice and reach the patient (translational research).
 
Legally it is organised as a public consortium where various institutions representing the Spanish General State Administration, the Spanish Autonomous Communities and other non-institutional organisations take part. It gathers a total of 58 Spanish research groups that share a common goal: the fight against neurodegeneration.
 
The funds managed by CIBERNED come mainly from the Spanish Government, namely from the Ministry of Economy and Competitiveness, which are channelled through the Carlos III Health Institute. However, CIBERNED can raise financial support from other foundations or research funds. In addition to basic and clinical research, CIBERNED aims to promote high-quality scientific dissemination and involve civil society in reducing the negative impact of neurodegeneration.
 
 
 
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