Orphan receptors have a similar structure to previously identified receptors, but their endogenous ligand has yet to be identified. Adopted receptors, or adopted orphans, have since had their endogenous ligand identified. These receptors interact with exogenous ligands, such as phytocannabinoids, which may act similarly to the intended endogenous ligand.
G-protein-coupled receptors (GPCR) represent the largest family of membrane receptors in the human body and play a critical role in various physiological processes. These receptors transmit signals from various external stimuli into cells, initiating a cascade of intracellular responses that affect functions such as sensory perception, mood, immune response, and homeostasis. Among these GPCRs, several are specifically responsive to cannabinoids, which are compounds found in cannabis and also produced endogenously as endocannabinoids.
Location and Function: GPR55 is expressed in various tissues, including the bone, brain (specifically the cerebellum), and small intestine.
Physiological Impacts: It plays a complex role in modulating blood pressure and bone density by promoting osteoclast cell function, which is crucial for bone reabsorption. However, GPR55 also has potential implications in pathologies such as cancer, as it can promote cancer cell proliferation.
Location and Function: This receptor is found in bones, spleen, lymph nodes, and testes.
Physiological Impacts: GPR18 regulates intraocular pressure, which is significant in conditions like glaucoma. It also has roles in cancer cell migration, suggesting a potential target for anti-metastatic therapies.
Location and Function: This receptor is located in the Hypothalamus-pituitary-adrenal axis and ovaries.
Physiological Impacts: GPR30 acts as an alternative estrogen receptor, playing a role in various estrogen-related functions and pathologies, potentially impacting conditions that are influenced by estrogen, such as certain breast cancers.
Location and Function: GPR119 is located in the pancreas and intestines and regulates food intake and metabolism.
Physiological Impacts: This receptor has been studied for its potential in treating disorders like diabetes and obesity, given its role in energy homeostasis and metabolic regulation.
Peroxisome Proliferator-Activated Receptors (PPAR) are a group of nuclear receptor proteins that function as transcription factors, regulating the expression of genes involved in various physiological processes. These include cellular differentiation, metabolism, and tumorigenesis. PPARs have been identified in various subtypes: PPARα, PPARβ/δ, and PPARγ, each having distinct roles and tissue distributions. Cannabinoids, both endogenous and phytocannabinoids, interact with these receptors, potentially offering therapeutic avenues for various diseases.
Location: Predominantly found in liver, kidney, heart, muscle, and adipose tissue.
Functions:
Metabolic Regulation: It plays a crucial role in lipid metabolism through processes like ketogenesis and regulates glucose metabolism by inhibiting glycolysis and promoting gluconeogenesis and glycogenesis.
Cardiovascular Health: Provides cardioprotection by inhibiting LDL cholesterol and macrophage foam cell formation, thereby reducing the risk of atherosclerosis.
Neuroprotection: Involved in neuroprotective actions, such as degrading amyloid-beta plaque and protecting against brain and heart ischemic injuries.
Analgesic and Anti-inflammation: Reduces pain and inflammation by inhibiting pro-inflammatory cytokines.
Location: Present in brain, adipose tissue, and skin.
Functions:
Metabolic Regulation: Regulates lipid metabolism.
Exercise Response: Expression increases with physical activity, linking it to exercise-induced metabolic benefits.
Antiproliferation: Exhibits antiproliferative effects that may prevent tumorigenesis.
Location: PPARγ1 is found in all tissues, while PPARγ2 is primarily in adipose tissue and PPARγ3 in macrophages, large intestine, and adipose.
Functions:
Metabolic Regulation: Influences glucose metabolism and increases insulin sensitivity. It also controls lipid metabolism and adipogenesis, important for managing obesity and diabetes.
Neuroprotection: It plays a role in neuroprotection by degrading amyloid-beta plaque associated with Alzheimer’s Disease
Cardiovascular Health: It is involved in cardioprotection working through vasorelaxation.
Antiproliferation: Offers potential for tumor regression in diseases like lung and breast cancer.
Anticonvulsant and Anti-inflammation: It has significant anti-inflammatory and anticonvulsive properties.