BML-190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: signalling via cAMP and inositol phosphates

FEBS Lett. 2003 Feb 11;536(1-3):157-60. doi: 10.1016/s0014-5793(03)00048-6.

Abstract

The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB(2) and CB(1) receptors, respectively. In HEK-293 cells stably expressing the human CB(2) receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB(2) receptor can interact productively with 16z44, a promiscuous G alpha(16/z) chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB(2) receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB(2) receptor acting via G alpha(i/o) and G alpha(q) family-coupled pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Indomethacin / analogs & derivatives
  • Indomethacin / pharmacology*
  • Inositol Phosphates / metabolism*
  • Ligands
  • Morpholines / pharmacology*
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Second Messenger Systems*

Substances

  • Inositol Phosphates
  • Ligands
  • Morpholines
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • indomethacin morpholinylamide
  • Colforsin
  • AM 251
  • Cyclic AMP
  • Indomethacin