We have continued to develop, refine and apply theoretical and statistical techniques which permit the characterization of mechanisms of hormone-receptor interaction. These techniques include optimized design to reduce the amount of experimental material required and maximize the utility of results obtained in each experiment. Analysis techniques utilizing non-linear least squares have been developed which allow simpler, more informative experiments to be performed. These techniques have been applied to the study of opiate receptor systems wherein a further characterization of subtypes of the mu receptor were obtained, and to characterization of subtypes of the kappa receptor in bovine adrenal medulla. A Monte-Carlo study of the validity of these statistical techniques was completed, showing them to be valid in the situation of mu-1, mu-2 opiate subtypes. A parametric means of characterization of asymmetric dose-response curves was developed and tested extensively on practical problems. An alternative, """"""""non-parametric"""""""", spline-based method of characterizing such curves, testing parallelism, and calculating potency is currently under development. A new statistical method for detecting non-randomness was developed and tested. This method is an alternative to the commonly used mean-square-successive differences test.
