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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-(N^δ-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 (K_d = 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.