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Free keywords:
Oxytocin; Oxytocin receptor; Oxytocin antagonist; Radioligand; Brain autoradiography; Myometrium; Tritium label; Peptide synthesis
Abstract:
A new tritiated oxytocin antagonist radioligand was synthesized by introducing a tritiated propionic acid residue into the free amino group of ornithine in position 8 of the parent peptide [1-(β-mercapto-β,β-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine, 4-threonine, 8-ornithine, 9-tyrosylamide]vasotocin (OTA), that was previously described. The tritiated compound [3H][1-(β-mercapto-β,β-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine, 4-threonine, 8-(Nδ-propionyl)-ornithine, 9-tyrosylamide]vasotocin ([3H]PrOTA) was obtained in good yield with high specific activity (100 Ci/mmol). [3H]PrOTA exhibited the same affinity (Kd = 0.8 nM) and selectivity for the myometrial oxytocin receptor as the iodinated antagonist [125I]OTA. Autoradiographic localization of oxytocin receptors in the rat brain showed specific binding sites for [3H]PrOTA within regions of the limbic system, the neocortex, and hypothalamus, which is consistent with the binding pattern obtained with [125I]OTA. The high specific activity in combination with the long half-life of tritium and its low radiotoxicity as compared to iodine-125 makes the new tritiated antagonist a valuable tool for pharmacological studies.
