Abstract
Since the work of McClintock and Hines, 1 it has been accepted generally that carnosine, β-alanyl-l-histidine, possesses oxytocic properties. They reported that this dipeptide produced a marked increase in the tonal and rhythmical contractions of strips of guinea pig uterus when such strips were immersed in Tyrode's or Ringer's solution containing the compound in a 1:2000 dilution. They stated that this action was qualitatively and quantitatively similar to that produced by histamine in dilutions of 1:100,000. The carnosine was, therefore, regarded as having one-fiftieth the oxytocic power of histamine. They furthermore reported in this study that the material isolated from muscle tissue behaved identically in all their experiments to the synthetic carnosine prepared by Baumann and Ingvaldsen 2 which had been placed at their disposal.
With the synthesis of d-carnosine 3 the possibility of studying the relationship of stereostructure to the physiological activity of carnosine was afforded. As the first step in this comparison, duVigneaud and Hunt 3 studied the effect of both optical isomers on the blood pressure. The d-carnosine in 20 times the dose of 1-carnosine was found to produce no perceptible decrease in the blood pressure of cats and rabbits under amytal and luminal anesthesia, thus demonstrating that the depressor action of carnosine depends upon the spatial configuration of the molecule.
In a continuation of this comparative study it was decided to test both isomers for oxytocic activity. Much to our surprise, however, when 1-carnosine was tried on the isolated virgin guinea pig uterus no oxytocic action could be detected. It was likewise found that the d-isomer was inert in this respect.
The method employed in testing for oxytocic activity was that outlined in the United States Pharmacopoeia for the assay of posterior pituitary extracts.
Get full access to this article
View all access options for this article.