The potent psychoactive properties of the cannabinoids and the identification and cloning of a cannabinoid receptor suggest they mimic endogenous compounds which modulate neural signals for mood, memory, movement and pain. Preliminary studies (below) have found that cannabinoids, potently and reversibly, inhibit N-type calcium channels via a Pertussis toxin-sensitive mechanism. The first part of the proposed study will extend these observations to acutely dissociated CNS neurons from regions rich in cannabinoid receptor with the aim to fully dissect the signal transduction pathway between the receptor and calcium channel. The second part proposes to develop polyclonal antibodies against the cannabinoid receptor using synthetic peptides based on the cDNA sequence of the cloned receptor. These antibodies will be used for anatomical, developmental, and biochemical characterization of the receptor. We anticipate that by utilizing two complementary techniques, one electrophysiological and the other immunological, we will substantially add to our knowledge of the cellular actions of the cannabinoids. This insight will be useful as it will both increase our understanding of a novel neurotransmitter system with marked behavioral effects, and will also allow a more rational assessment of the use of cannabinoids as therapeutic agents.
