Arginine vasopressin antagonism of oxytocin-stimulated PGE2 release from rabbit amnion cells and the activities of thioanalogs of oxytocin and arginine vasopressin
Czaja, M.; Kruszyński, M.; Hinko, A.; Soloff, M.S.
Polish Journal of Pharmacology 46(5): 429-437
1994
ISSN/ISBN: 1230-6002 PMID: 7894530 Document Number: 435066
Using rabbit amnion membranes devoid of arginine vasopressin receptors, we have shown that arginine vasopressin acts as a partial agonist and oxytocin antagonist. We examined peptides with modifications in position 8 to determine the basis for partial agonism/antagonism. The 8-thioanalog of oxytocin had about 40% of oxytocin activity in eliciting PGE-2 release by amnion cells and a corresponding 40% affinity for oxytocin binding sites on amnion membranes. Arginine vasotocin, which has arginine at the position 8 and about 90% homology with arginine vasopressin also acted as a full agonist. These results suggest that determination of the oxytocin antagonist activity of arginine vasopressin is largely dependent on the amino acid at position 3. We also synthesized the 8-thioanalog of arginine vasopressin, which had a very low affinity for arginine vasopressin binding sites in rat liver (V-1 receptors) and rat kidney medulla (V-2 receptors) membranes. These Findings suggest that arginine vasopressin receptors are much more sensitive to modifications of the peptide bond between positions 8 and 9 than are oxytocin receptors.