Dose-response behavior on the isolated rat uterus of oxytocin analogs with modifications at binding sites.

The dose-response behavior on the in vitro rat uterus of analogs of oxytocin with modification at sites in the molecule which have been predicted to contribute to the binding of the peptide to the smooth muscle receptor have been studied. Dose-response curves of [7-(3,4-dehydroproline)]oxytocin, [7-glycine]oxytocin, [7-alanine]oxytocin, deamino-[7-glycine]oxytocin and [4-threonine,7-glycine]oxytocin were determined and compared with that of oxytocin. The authors found that neither the slope of the curves nor the maximal response obtained for any of the analogs differed significantly from the hormone. The uterotonic potencies of the analogs corresponded to the relative positions along the concentration axis of their dose-response curves and to their affinities as determined by their pD2 values. The authors tentatively concluded that differences in uterotonic potencies of these analogs are in fact the result of differences in their affinity for the uterine receptor. The experimental identification of position 7 of neurohypophyseal peptides as a hormone-receptor binding site corroborates such a proposed role for the side chain of this residue based on earlier conformation-activity considerations.