The proposed project on the discovery of multiple chromosomal transcripts for opioid receptors was terminated with the departure of our postdoctoral fellow in June, 1998. Until that time, evidence accumulated which strongly suggested that the brain of Mummichog, a diploid teleost, contained two distinct transcripts for each of the opioid receptors, delta, mu and kappa. Partial sequence analyses indicated that they differed to a greater degree from each other than to that of the human receptor cDNA. These results should be completed as they clearly shed light on the possibility that the pharmacologically distinct receptor subtypes reside in unique protein molecules. Another project dealing with a model system for studying possible involvement of human MDR-1 (multi- drug resistance protein-1) in passage of peptides through the intractable blood-brain barrier utilized cDNA stably transfected into a fibroblast cell line. In fact, a correlation was observed between the hydrophobicity of a series of N- and C-terminally modified delta-opioid antagonists containing the Dmt-Tic pharmacophore and its ability to inhibit the activity of this membrane- bound protein. The data should enhance our knowledge for the design of new opioid analogues in the treatment of human of drug addiction, alcohol dependency and immunosuppression.
