A PHARMACOLOGIC ANALYSIS ON THE SIGNIFICANCE OF THE CHEMICAL FUNCTIONAL GROUPS OF OXYTOCIN TO ITS OXYTOCIC ACTIVITY AND ON THE EFFECT OF MAGNESIUM ON THE IN VITRO AND IN VIVO OXYTOCIC ACTIVITY OF NEUROHYPOPHYSIAL HORMONES

¹ Department of Biochemistry, Cornell University Medical College, New York, New York

The oxytocin molecule contains six chemical functional groups: an amino group, a phenolic hydroxyl group, three carboxamide groups and a disulfide bond. We have determined the significance of each of these functional groups to the oxytocic action of the hormone with respect to affinity and intrinsic activity by analyzing the cumulative dose-response curves of a series of oxytocin analogs lacking a particular functional group. Our results indicate that the phenolic hydroxyl group and the carboxamide groups in positions 5 and 9 are involved in both the affinity and the intrinsic activity, whereas the carboxamide group in position 4 affects the affinity of the hormone molecule. Analogs lacking these functional groups have decreased affinity and/or intrinsic activity. The amino group exerts no significant influence. The absence of the amino group may actually increase the affinity of the oxytocin molecule for the uterine receptors. Indirect evidence suggests that the disulfide bond is important but not essential to the activity of the hormone. We have also studied the potentiating effect of magnesium on the oxytocic activity of these analogs in vitro and have determined the in vivo oxytocic activity of these analogs and lysine-vasopressin. Our results suggest that the oxytocic effect in vivo may also be influenced by the normal serum magnesium.