G-Protein Coupled Receptor

G-protein coupled receptors (GPCRs) are a class of membrane receptors that transduce extracellular signal into intracellular events. Many hormones and neurotransmitters act on GPCRs to produce their biological effects. Upon binding its agonist, GPCRs will activate specific G proteins, which in turn, modulate other intracellular effectors such as enzymes or ion channels.

Besides sharing a common signal transduction mechanism via G proteins, all GPCRs share one common structural feature, possessing a transmembrane domain with seven helixes. The transmembrane domain is crucial in converting the binding energy of GPCR agonists into intracellular second messenger signaling. A particular GPCR may interact with one of several major classes of G-proteins, leading to a change in intracellular cAMP level, calcium level, potassium level, or the level of other second messengers.

GPCRs are important in treating obesity, because many medicinal compounds act on GPCRs directly or indirectly to exert their therapeutic effects. For example, sibutramine, known by the trade name Meridia, inhibits serotonin transporter and norepinephrine transporter, leading to increase of serotonin and norepinephrine which in turn activate G-protein coupled serotonin receptors and adrenergic receptors. Ephedrine acts indirectly on adrenergic receptors by releasing norepinephrine from nerve terminals. These biological events ultimately serve to suppress appetite. New experimental anti-obesity agents are being developed to target GPCRs directly, including cannabinoid receptor inverse agonists/blockers and serotonin 5HT2c agonists.