Structural Requirements for the Action of Neurohypophyseal Hormones upon the Isolated Amphibian Urinary Bladder

The response of the isolated amphibian urinary bladder to thirty-four structural analogs of arginine vasotocin was determined in an effort to define the physiological significance of specific structural groups on the hormone molecule. All but one of the analogs tested possessed full intrinsic activity in this system but varied greatly in their affinity for the receptor site. An analysis of the effect of changes in hydrogen ion concentration upon the response of the bladder to oxytocin was performed in order to determine the number and nature of the ionizable groups involved in hormone receptor interaction. Two ionizable groups with apparent pK's of 7.1 and 7.75 were found to be important in determining the magnitude of the hormonal response. On the basis of the results it was postulated that hormone-receptor interaction can be considered a two-step process: (a) The binding or attachment of hormone to receptor site through ionic, hydrogen, and hydrophobic bonds and (b) a disulfide interchange reaction between hormonal disulfide and receptor sulfhydryl. The latter step is considered to be the reaction which initiates the chain of events leading to the observed change in permeability.