Detection of cannabinoid receptors by photoaffinity labelling.
A novel [125I]-labelled photoaffinity ligand designed to detect cannabinoid binding sites has been used in mouse brain preparations and in cultured S49 mouse lymphoma cells. The ligand, 2-iodo-5'-azido-delta 8-THC, shows a high affinity for sites in both brain (Kd = 5.60 pM) and whole cell (Kd = 9.38 pM) systems. Photolabelling studies with brain samples revealed the existence of four ligand-protein adducts, of estimated molecular weights 85.5, 62.1, 30.0 and 25.5 kDa, that were diminished by prior exposure to 8 microM THC. A similar study with S49 cells gave adducts with apparent molecular weights of 62.1, 34.4, 16.9 and 13.5 kDa. The ligand produces a typical cannabinoid cataleptic response in mice suggesting that possibly one or more of the binding sites may be involved in some of the receptor mediated actions of THC.
Burstein
S H
SH
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01655.
Audette
C A
CA
Charalambous
A
A
Doyle
S A
SA
Guo
Y
Y
Hunter
S A
SA
Makriyannis
A
A
D000345:Affinity Labels / Q000378:metabolism*; D000818:Animals; D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*
D000345:Affinity Labels; D001386:Azides; D008024:Ligands; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C068306:2-iodo-5'-azido-delta(8)-tetrahydrocannabinol; D013759:Dronabinol