Comparison of cumulative and individual dose-response curves on the rat uterus of neurohypophyseal peptides

Abstract

The dose-response behavior on the isolated rat uterus of the neurohypophyseal hormones oxytocin, lysine vasopressin and a number of analogs was compared using either the cumulative dose-response procedure or the individual dose response method. Although the cumulative assay method has certain advantages, it can with this category of peptides only be used with caution as revealed by the adverse effects on the intrinsic activity of some of the peptides studied. In the course of our studies on the action of neurohypophyseal hormones and synthetic analogs on rat uterine tissue in vitro , we repeatedly observed that certain peptides exert a potentiating or inhibiting effect on themselves, on the hormones or on the analogs. This phenomenon created doubts as to the general applicability of the cumulative dose-response technique where the analog might also have an effect on subsequent doses administered additively. This effect would be most significant at the concentration range where intrinsic activity is determined. In order to investigate this point the cumulative dose-response curves of a number of neurohypophyseal peptides were compared with dose-response curves obtained by the normal method with draining and washing after each injection.