GPCR introduction

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G Protein Coupled Receptors (GPCRs) are a large family of transmembrane receptors that control a vast array of cellular processes. GPCRs are bound to G Proteins which can be monomeric (single subunit) or heterotrimeric and made up of α, β and γ subunits. Gα subunits can be roughly divided into three functional groups:

  • Gαs/i/o (stimulatory/inhibitory/other) regulate cAMP levels which are a general indicator of cellular energy and activity levels and regulate hundreds of secondary processes.
  • Gαq11 regulate PLCβ and consequently Ca2+ levels which are also involved in hundreds of secondary processes.
  • Gα12/13 which regulate cytoskeleton and cell division associated processes.

Upon activation of the GPCR, the α and β/γ subunits dissociate from the receptor and execute their functions. There are multiple human genes coding for different α, β and γ subunits and many of these genes have alternative splice variants giving rise to 1000s of unique GPCRs and probably as many different cellular functions. In addition, GPCRs can form complexes with other receptors or ion channels, enhancing their functional diversity even further. In short, GPCRs are complex, multi-unit, proteins that control a range of the most basic and critical cellular functions such as energy metabolism, ionic balance and cell division. Most cannabinoid receptors identified so far are GPCRs. This explains why:

  • There is so much cross-functionality between cannabinoids and/or cannabinoid receptors.
  • cannabinoid receptor are involved in such a wide variety of cellular functions.
  • cannabinoids have such tremendous therapeutic potential.
  • It is so difficult to ascribe any particular cellular or therapeutic function to any particular one cannabinoid
  • Carefully balanced cocktails of cannabinoids are more likely to give optimal therapeutic effect and minimal complications than any one cannabinoid.

Chemical Name

G Protein Coupled Receptors

IUPHAR entry

Wikipedia Entry