Role of intracellular loops of cannabinoid CB(1) receptor in functional interaction with G(alpha16)

FEBS Lett. 2002 Jul 3;522(1-3):130-4. doi: 10.1016/s0014-5793(02)02917-4.


The cannabinoid CB(1) but not the CB(2) receptor was demonstrated to couple via G(alpha16) to activate phospholipase C after co-expression in COS7 cells. Chimeric CB(1)/CB(2) receptors were used as a model to study receptor-G(alpha16) interaction. Sequences of the second and third intracellular loops and the carboxy-terminus were substituted from the CB(1) into the CB(2) receptor. Only the triple mutant with all three regions replaced activated phospholipase C to a similar extent as the CB(1) receptor, suggesting that all three intracellular regions are required for interacting with G(alpha16). Several sub-domains within the third intracellular loop were identified for receptor-G(alpha16) interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Cannabinoids / metabolism*
  • Chlorocebus aethiops
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Intracellular Fluid / metabolism
  • Molecular Sequence Data
  • Receptors, Cannabinoid
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism*
  • Sequence Homology, Amino Acid
  • Type C Phospholipases / metabolism


  • Cannabinoids
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Type C Phospholipases
  • G protein alpha 16
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins