Over the past two years this laboratory had been investigating the binding of various neurotransmitters (5-HT, dopamine, NE) to their high affinity sites on isolated (lysed) synaptosomal membranes prepared from whole rat brain. In addition to binding measurements we have been following the production of cyclic nucleotides as a consequence of transmitter binding and the effects of various CNS active drugs on both processes. During the course of this work we have uncovered four (4) definitive 5-HT binding sites which appear to be associated with their own adenylate cyclase activity. We have found that the effects of drugs (e.g. methadone) on both binding and nucleotide production is much more complex than has been previously reported. From our data we have identified the reuptake site. The effects of antiprostaglandin agents on the two processes would suggest that PG's may be involved in the coupling of transmitter binding to cyclic nucleotide production. We have also found that the hallucinogenic indolealkylamine dimethyltryptamine (DMT) is a normal constituent of brain tissue and as such has activity which may suggest that it plays a role in the regulation of neuronal activity. In our study of dopamine binding we have also identified two distinct binding sites. One site is blocked by the antipsychotic drugs while the highest affinity site is not. We have also developed a flow dialysis technique for the in vitro study of neurotransmitter release and for the study of specific drug effects on this process. BIBLIOGRAPHIC REFERENCES: Pagel, J., Christian, S.T>, Quayle, E., and Monti, J. A serotonin sensitive adenylate cyclase in mature rat brain synaptosomes. Life Science, 19, 819-824, 1976. Monti, J., Christian, S.T., Shaw, W.A., and Finley, W. A fluorescent phosphatidylcholine derivative for use as a membrane probe. Proc. Am. Soc. Neurochemistry 8, 25 (1977).
NIH ExPorter
NIH ExPorter