gpr55 receiver

The GPR55 receptor is a membrane protein that plays an important role in various biological and physiological functions.

It is involved in pain modulation, blood pressure regulation, and immune response, among others.

This introduction presents an overview of the GPR55 receptor, discussing its definition, function, and importance in the biological system.

Definition and function of GPR55 receiver

The GPR55 receptor, also known as the orphan receptor, is a membrane protein that belongs to the G protein-coupled receptor (GPCR) family.

It is mainly expressed in the central and peripheral nervous system, as well as in certain immune cells.

The GPR55 receptor is involved in the regulation of various physiological processes, such as pain modulation, blood pressure regulation, and immune response.

Importance of GPR55 receptor in biological system

The GPR55 receptor is considered a key player in the regulation of various biological functions. It is involved in cell signaling and the transmission of information between cells.

Additionally, it is being studied for its potential role in the treatment of various diseases, such as neurodegenerative diseases and cancers.

The importance of the GPR55 receptor in the biological system makes it a promising research subject for the development of new therapies.

Structure and location of the GPR55 receptor

The GPR55 receptor is a membrane protein composed of seven transmembrane domains, which are characteristic of the GPCR family.

It also has extracellular and intracellular domains, which are involved in binding to specific ligands and activation of intracellular signaling pathways.

1. Membrane protein

The GPR55 receptor is anchored in the cell membrane and has a specific three-dimensional structure.

This structure allows it to recognize and bind to specific ligands, such as lipids and endocannabinoids, to modulate various cellular functions.

2. Specific connections

The GPR55 receptor interacts with various ligands, such as lipids, endocannabinoids, and synthetic cannabinoids.

These interactions result in receptor activation and transmission of intracellular signals, thereby modulating various biological functions.

Cellular and tissue localization

The GPR55 receptor is expressed in various tissues and cells in the human body, including the central nervous system, immune system, and endothelial cells.

1. Central nervous system

The GPR55 receptor is widely expressed in the brain, particularly in regions involved in pain regulation, memory and learning.

It is also present in the spinal cord and dorsal root ganglia, where it plays a role in transmitting pain signals.

2. Immune system

The GPR55 receptor is also expressed in certain immune cells, such as B and T lymphocytes, macrophages, and dendritic cells.

It is involved in the regulation of the immune response and the modulation of inflammation.

Involvement of the GPR55 receptor in diseases

The GPR55 receptor is being studied for its potential role in the development and progression of various diseases, including neurodegenerative diseases and cancers.

This section discusses the involvement of the GPR55 receptor in these diseases and presents scientific sources to support this information.

A. Neurodegenerative diseases

1. Multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system. Studies have shown that the GPR55 receptor is involved in the regulation of neuroinflammation and neuroprotection in MS.

A study carried out by Al-Ghezi et al. (2017) demonstrated that modulation of the GPR55 receptor could have therapeutic potential for MS by reducing inflammation and protecting neurons ¹ .

2. Alzheimer's disease

Alzheimer's disease is a neurodegenerative disease characterized by the progressive loss of memory and cognitive functions.

The GPR55 receptor is expressed in regions of the brain affected by Alzheimer's disease, and studies suggest that it may play a role in the progression of this disease.

A study conducted by Kotsikorou et al. (2011) revealed that specific ligands of the GPR55 receptor could have therapeutic potential for the treatment of Alzheimer's disease by modulating neuroinflammation and neuroprotection ² .

B. Cancers

1. Brain cancer

The GPR55 receptor is expressed in various types of cancers, including glioblastoma, a very aggressive type of brain cancer.

A study carried out by Andradas et al. (2011) showed that activation of the GPR55 receptor promotes the proliferation and survival of glioblastoma cells, suggesting that targeting this receptor could offer a therapeutic approach for the treatment of this cancer ³ .

2. Breast cancer

The GPR55 receptor is also involved in the progression of breast cancer.

A study conducted by Ford et al. (2010) revealed that expression of the GPR55 receptor is associated with increased proliferation of breast cancer cells and greater tumor aggressiveness.

This study suggests that the GPR55 receptor could be a potential therapeutic target for the treatment of breast cancer ⁴ .

Other potential implications of the GPR55 receptor

Besides the neurodegenerative diseases and cancers mentioned previously, the GPR55 receptor has also been studied for its potential role in other medical conditions.

This section discusses two of these conditions, namely metabolic disorders and pain, and presents scientific sources to support this information.

A. Metabolic disorders

1. Obesity

Obesity is a major health problem that can lead to various complications, such as type 2 diabetes and cardiovascular diseases.

The GPR55 receptor is expressed in adipose tissues and could play a role in the regulation of energy metabolism. A study conducted by Romero-Zerbo et al. (2011) revealed that activation of the GPR55 receptor promotes lipogenesis and weight gain in mice.

This study suggests that targeting the GPR55 receptor could offer a therapeutic approach for the prevention and treatment of obesity ⁵ .

2. Diabetes

Diabetes is a chronic disease characterized by hyperglycemia and impaired metabolism of carbohydrates, lipids and proteins.

Studies have shown that the GPR55 receptor is involved in the regulation of insulin secretion and insulin sensitivity.

A study by McKillop et al. (2013) demonstrated that modulation of the GPR55 receptor could have therapeutic potential for the treatment of diabetes by improving islet β cell function and increasing insulin sensitivity ⁶ .

B. Pain

The GPR55 receptor is expressed in sensory neurons and has been studied for its potential role in pain modulation.

A study conducted by Staton et al. (2008) revealed that activation of the GPR55 receptor increases the release of pain-related peptides, such as substance P and calcitonin gene-related peptide, in sensory neurons.

This study suggests that the GPR55 receptor could be a potential therapeutic target for the treatment of chronic pain ⁷ .

In summary, the GPR55 receptor is implicated in various diseases and medical conditions, including neurodegenerative diseases, cancers, metabolic disorders, and pain.

Research continues to explore the role of the GPR55 receptor in these conditions and its potential as a therapeutic target for the development of new treatments.

Research and development of drugs targeting the GPR55 receptor

A. Scientific advances

1. Mechanisms of action

The mechanisms of action of the GPR55 receptor are still being studied. The GPR55 receptor has been shown to be activated by various ligands, such as lipids and cannabinoids , and to be involved in intracellular signaling via G protein activation and inositol phosphate production ⁸ .

Further research is needed to elucidate the precise mechanisms of action and signaling pathways of the GPR55 receptor.

2. Therapeutic potential

The therapeutic potential of the GPR55 receptor is being explored in various fields, including neurodegenerative diseases, cancers, metabolic disorders and pain.

Modulation of the GPR55 receptor could offer new therapeutic approaches for these medical conditions, but additional research is needed to evaluate the effectiveness and safety of drugs targeting this receptor.

B. Drugs undergoing clinical trials

1. Preclinical phase

Several compounds targeting the GPR55 receptor are currently in preclinical development. For example, ML184 (CID-2440433) is a selective GPR55 receptor agonist that has shown promising activity in preclinical models of neuropathic pain ⁹ .

Other compounds, such as GPR55 receptor antagonists, are also being investigated for their therapeutic potential in various diseases.

2. Clinical phase

To date, no drug specifically targeting the GPR55 receptor has reached clinical phase testing.

However, given the promising therapeutic potential of the GPR55 receptor, it is likely that drugs targeting this receptor will enter the clinical phase in the near future.

Additional Resources and Information

Research articles

1. Scientific journals

The following scientific journals regularly publish research articles on the GPR55 receptor and its therapeutic potential:

• British Journal of Pharmacology
• Journal of Biological Chemistry
• Molecular Pharmacology
• Neuropharmacology

2. Recent publications

Here are some recent publications on the GPR55 receptor:

• Kotsikorou, E., Madrigal, KE, Hurst, DP, Sharir, H., Lynch, DL, Heynen-Genel, S., ... & Abood, ME (2011). Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands. Biochemistry, 50(25), 5633-5647. https://doi.org/10.1021/bi2000899
• AlSuleimani, Y.M., & Al Mahruqi, A.S. (2017). The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterology & Motility, 29(10), e13108. https://doi.org/10.1111/nmo.13108

Research organizations and institutions

1. Universities

Several universities are conducting research on the GPR55 receptor, including:

• University of Edinburgh (UK)
• University of Nottingham (UK)
• University of California, Irvine (United States)

2. Research laboratories

The following research laboratories focus on the study of the GPR55 receptor and its therapeutic implications:

• Cannabinoid Research Laboratory, University of Edinburgh
• Molecular Pharmacology Laboratory, University of Nottingham
• G Protein Coupled Receptor Research Laboratory, University of California, Irvine

Future prospects and challenges in GPR55 receptor research

Research on the GPR55 receptor has revealed its involvement in various diseases and medical conditions, offering promising therapeutic potential.

However, there are still many challenges and prospects for future research on GPR55 receptor. This section addresses some of these challenges and perspectives.

Elucidation of the mechanisms of action of the GPR55 receptor

A major challenge in GPR55 receptor research is understanding its precise mechanisms of action.

Although progress has been made in understanding the involvement of the GPR55 receptor in various diseases, the precise molecular and cellular mechanisms by which it exerts its effects remain to be elucidated.

Further studies are needed to understand the signaling pathways involved and the interactions with other receptors and proteins.

Development of selective ligands for the GPR55 receptor

The development of selective ligands for the GPR55 receptor is crucial to explore its therapeutic potential.

Selective ligands make it possible to study the specific effects of the GPR55 receptor more precisely and to minimize off-target effects.

Future research should focus on the design and synthesis of novel selective GPR55 receptor ligands, as well as the evaluation of their efficacy and safety in preclinical and clinical models.

Evaluation of long-term effects of GPR55 receptor modulation

Most studies of the GPR55 receptor have been performed in the short term, and the long-term effects of GPR55 receptor modulation remain largely unknown.

Evaluating the long-term effects of GPR55 receptor activation or inhibition is essential to determine the safety and effectiveness of therapies targeting this receptor.

Long-term studies in animal models and clinical trials are needed to address this question.

Exploring the therapeutic potential of the GPR55 receptor in other diseases

The GPR55 receptor has been studied primarily in the context of neurodegenerative diseases, cancers, metabolic disorders and pain.

However, it could also be involved in other illnesses and medical conditions.

Future research should explore the role of the GPR55 receptor in other areas, such as immunology, mental health, and cardiovascular disease, to evaluate its therapeutic potential in a broader range of conditions.

In conclusion, the GPR55 receptor offers promising therapeutic potential in various diseases and medical conditions. However, there are still many challenges and prospects for future research on this receptor.

In-depth understanding of the mechanisms of action of the GPR55 receptor, development of selective ligands, evaluation of long-term effects and exploration of its therapeutic potential in other diseases will help to fully realize the potential of this receptor as a as a therapeutic target.

Sources:

1. Al-Ghezi, Z.Z., Busbee, P.B., Alghetaa, H., Nagarkatti, P.S., & Nagarkatti, M. (2017). Combination of cannabinoids, Δ9-tetrahydrocannabinol and cannabidiol, ameliorates experimental multiple sclerosis by suppressing neuroinflammation through regulation of miRNA-mediated signaling pathways. Frontiers in Immunology, 8, 1449. https://doi.org/10.3389/fimmu.2017.01449 ↩

2. Kotsikorou, E., Madrigal, KE, Hurst, DP, Sharir, H., Lynch, DL, Heynen-Genel, S., ... & Reggio, PH (2011). Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands. Biochemistry, 50(25), 5633-5647. https://doi.org/10.1021/bi2000899 ↩

3. Andradas, C., Caffarel, MM, Pérez-Gómez, E., Salazar, M., Lorente, M., Velasco, G., ... & Sánchez, C. (2011). The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. Oncogene, 30(2), 245-252. https://doi.org/10.1038/onc.2010.402 ↩

4. Ford, LA, Roelofs, AJ, Anavi-Goffer, S., Mowat, L., Simpson, DG, Irving, AJ, ... & Ross, RA (2010). A role for L-α-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. British Journal of Pharmacology, 160(3), 762-771. https://doi.org/10.1111/j.1476-5381.2010.00743.x ↩

5. Romero-Zerbo, SY, Rafacho, A., Díaz-Arteaga, A., Suárez, J., Quesada, I., Imbernon, M., ... & Bermúdez-Silva, FJ (2011). A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans. Journal of Endocrinology, 211(2), 177-185. https://doi.org/10.1530/JOE-11-0166 ↩

6. McKillop, AM, Moran, BM, Abdel-Wahab, YHA, & Flatt, PR (2013). Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice. British Journal of Pharmacology, 170(5), 978-990. https://doi.org/10.1111/bph.12356 ↩

7. Staton, PC, Hatcher, JP, Walker, DJ, Morrison, AD, Shapland, EM, Hughes, JP, ... & Patel, S. (2008). The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Bread, 139(1), 225-236. https://doi.org/10.1016/j.pain.2008.04.006 ↩

8. Henstridge, C.M., Balenga, NA, Ford, LA, Ross, RA, Waldhoer, M., & Irving, AJ (2009). The GPR55 ligand L-α-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation. The FASEB Journal, 23(1), 183-193. https://doi.org/10.1096/fj.08-108670 ↩

9. Morales, P., Goya, P., Jagerovic, N., & Hernandez-Folgado, L. (2016). Allosteric modulators of the CB1 cannabinoid receptor: a structural update review. Cannabis and Cannabinoid Research, 1(1), 22-30. https://doi.org/10.1089/can.2015.0004 ↩