The psychoactive properties of cannabinoids have been described in man and investigated in a variety of animal models. Association of these effects with neurotransmitter systems has been investigated with limited success. In vitro studies have failed to elucidate the mechanism of cannabinoid action at the neuroneal level. Some investigators have concluded that the lipid bilayer of the neuronal membrane is the primary site of action of the canabinoids, and that it is unnecessary to invoke the existence of a specific cannabinoid receptor. An argument against this is that the only physiological action of cannabinoids that """"""""partial anesthetics"""""""" produce is the catalepsy response. Furthermore, the relevance of these membrane effects to the psychoactivity of cannabinoids is questionable due to the equal efficacy and similar potency of nonpsychoactive compounds. Adenylate cyclase is one plasma membrane enzyme system in which cannabinoid effects have been noted. However, it is difficult to interpret studies of hormone-regulated cyclic AMP accumulation in brain because of the variety of cell types and the multiple neurotransmitter receptors putatively associated with adenylate cyclase in brain. Study of this interaction at the level of a neuronal cell is necessary to provide a functional basis with which to search for a specific cannabinoid receptor, if one exists.
The specific aims of this study are to evaluate properties of cannabinold inhibition of adenylate cyclase in enuroblastoma membrane preparations and to characterize the cannabinoid effects intact neuroblastoma cells.
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