Arginine vasopressin antagonism of oxytocin-stimulated PGE2 release from rabbit amnion cells and the activities of thioanalogs of oxytocin and arginine vasopressin.
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 PGE2 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 (V1 receptors) and rat kidney medulla (V2 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.
Czaja
M
M
Department of Chemistry, University of Gdańsk, Poland.
Kruszyński
M
M
Hinko
A
A
Soloff
M S
MS
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000650:Amnion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D001665:Binding Sites; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism; D014668:Vasotocin / Q000378:metabolism / Q000494:pharmacology
D000596:Amino Acids; D010455:Peptides; D001127:Arginine Vasopressin; D010121:Oxytocin; D013455:Sulfur; D015232:Dinoprostone; D014668:Vasotocin