The Endocannabinoid System
Virodhamine is an endocannabinoid compound discovered in,
A system that maintains balance or homeostasis from the time that a person is born. Promoting general well being. The endocannabinoid system can help with neurological shortcomings, musculoskeletal problems, inflammatory and immune issues. The human body produces its own cannabinoids, such as 2-Arachidonoyl(2-AG), Virodhamine(O-AEA) and Anandamide(AEA). Because they are produced within the body, they are termed endocannabinoids.
The endocannabinoid system uses retrograde signaling to send endocannabinoids from the postsynaptic neuron( the neuron receiving a signal) to the presynaptic neuron(the one that sent the signal). To illustrate, let’s say a presynaptic neuron in the brain is secreting glutamate to a postsynaptic neuron. The glutamate will bind to the receptors in the postsynaptic neuron and cause calcium gated ion channels to open. The result is that calcium will begin to accumulate inside the neuron that received the signal, the postsynaptic neuron. This is normal during times of high activity. Now, because of the accumulation of substantial calcium in the postsynaptic neuron, endocannabinoids will be synthesized from lipids in the membrane of the postsynaptic neuron, they will be secreted, and then they will bind to the G Protein coupled receptors of the presynaptic neuron. The result follows.
How do the receptors of the ECS work
The receptors are of the endocannabinoid system that are most highly regarded are the CB1 and CB2 receptors. The CB1 receptor is primarily localized in the brain (i.e. Hippocampus, Cerebrum, Cerebellum). The CB2 receptor is primarily localized in the peripheral aspect of the body (i.e. GI tract, tonsils, spleen, immune cells). Now, both the CB1 & CB2 receptors are classified as G-Protein coupled receptors. They are receptors which have seven helices, seven protein columns that crosses the cellular membrane seven times like a snake. These receptors have three subunits, called the alpha, beta, and gamma subunits.
G-Protein coupled receptors are capable of binding all kinds of molecules such as light reactive ones, hormones, pheromones. G- Protein coupled receptors are capable of regulating a substantial array of mechanisms in the body such as taste, growth, and vision.
The body has an immense quantity of G-Protein Coupled Receptors, all of which bind different ligands. Those that bind exogenous or endogenous cannabinoids are called CB1 & CB2 receptors. The way that CB1 & CB2 receptors work is that once an endocannabinoid binds to the active site of the receptor, GDP is exchanged for it’s energetic superior, Guanosine Triphosphate. Making it unstable to hold. As a result, the alpha subunit, paired with the GTP, and the beta-gamma dimer no longer bound to the alpha subunit are both available to move laterally into the cell. Now, the subunits of the G-Protein will dissociate from the complex and embark on a journey within the cell to relay that specific signal. However, when this GTP is hydrolyzed back to GDP, the subunits once again assume the form of an inactive heterotrimer, and associate with the entire inactive GPCR. In this way, G proteins work like a switch — turned on or off by signal-receptor interactions on the cell’s surface.
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CB1 receptor antagonist
Virodhamine is a part of the endocannabinoid system because it is responsible for taking over the role of antagonism at the CB1 receptor, while still stimulating the CB2 receptor for action. Somes endocannabinoid transmitters are also the name that has been given to these molecules for their incredible impact on the homeostatic conditions of the body. In vivo activity of virodhamine in the bodies of mice has shown that the core body temperature was lower in mice administered virodhamine compared to control mice. In fact, the concentration of virodhamine in the peripheral tissues of the body is two fold – nine fold higher than in the brain. Scientists believe this to be because of the higher quantity of CB2 receptor dispersion in the periphery of the body.
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