In ongoing work in the department of Natural Products, Hebrew University Medical School, Jerusalem, 3 fractions of porcine brain have been found to bind to the cannabinoid receptor and to produce a concentration - dependent inhibition of the electrically evoked twitch response of the mouse vas deferens. The cannabinoid receptor work employed a novel, highly sensitive probe developed in Jerusalem. The main objective of the research proposal is to obtain in pure form, elucidate the structures of the 3 (or more) endogenous cannabinoids present in porcine brain and make them available for further investigations through synthesis. One of the components is already available in ca 80% purity. The methodology in the isolation work will be column, thin layer (normal and reverse phase), gas and high-pressure liquid chromatography. The structure elucidation will make use mainly of mass spectrometry and, if enough material is isolated, of NMR techniques. The synthetic procedures will have to be decided upon when the structures of the active compounds are elucidated. This research may help understand the mode of action of Cannabis, its receptor and mediators.
Rhee, M H; Vogel, Z; Barg, J et al. (1997) Cannabinol derivatives: binding to cannabinoid receptors and inhibition of adenylylcyclase. J Med Chem 40:3228-33 |
Sheskin, T; Hanus, L; Slager, J et al. (1997) Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor. J Med Chem 40:659-67 |
Mechoulam, R; Ben-Shabat, S; Hanus, L et al. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83-90 |
Pertwee, R; Griffin, G; Hanus, L et al. (1994) Effects of two endogenous fatty acid ethanolamides on mouse vasa deferentia. Eur J Pharmacol 259:115-20 |
Mechoulam, R; Hanus, L; Martin, B R (1994) Search for endogenous ligands of the cannabinoid receptor. Biochem Pharmacol 48:1537-44 |