Beta-2 adrenergic receptor: Difference between revisions

=='''Cannabinoid Receptor 1 (CB1)'''==

In neurons, CB1 is presynaptic and modulates neurotransmitter release by retrograde signaling, meaning the message travels from postsynaptic neurons to presynaptic neurons. The portion of the receptor with eight alpha helices spans the membrane, giving an active site on the extracellular portion of the receptor. This active site is filled with <scene name='71/716602/Polar_side_chains/1'>polar</scene> side chains, allowing for hydrogen bonding of the <scene name='71/716602/Ligand_bound/1'>ligand</scene>, which is nonpolar. When the agonist binds to CB1, a conformational change occurs in the receptor. The beta sheet and other two alpha helices are intracellular, and after the conformational change this portion produces a binding site for a heterotrimeric G-protein <ref name="k2" />. This heterotrimeric protein is bound to guanosine diphosphate (GDP), but the interaction causes an exchange of GDP to guanosine triphosphate (GTP), which catalyzes the dissociation of the heterotrimeric G-protein and promotes several signaling cascades. This activity inhibits intracellular cyclic AMP (cAMP) production, opening of some voltage gated calcium channels, and activates some potassium channels <ref name="k2" />. The inhibition of opening calcium channels and the activation of potassium channels, which both cause hyperpolarization, make it more difficult to excite an action potential in a neuron. There is an increase in the amount of dopamine present in the brain, which promotes the brain reward system. This is due to inhibition of dopaminergic neurons that would take up this dopamine. The agonists cause an inhibitory effect on neuronal function <ref name="k2" />. In contrast to cannabis, K2 is synthetic and contains multiple SCBs that participate in drug-drug interactions. These interactions promote potency of synergistic effects, but they also contribute negative side effects <ref>PMID: 24084047</ref>.