title: A new tritiated oxytocin receptor radioligand--synthesis and application for localization of central oxytocin receptors.
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-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine, 4-threonine, 8-ornithine, 9-tyrosylamide]vasotocin (OTA), that was previously described. The tritiated compound [3H][1-(beta-mercapto-beta,beta-cyclo-pentamethylene propionic acid), 2-(O-methyl)-tyrosine, 4-threonine, 8-(N6-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.
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D009215:Myometrium / Q000378:metabolism; D009928:Organ Specificity; D011247:Pregnancy; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D018045:Receptors, Oxytocin / Q000032:analysis* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000032:analysis* / Q000378:metabolism; D014316:Tritium; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; C096587:vasotocin, d(CH2)5-O--methyl-Tyr(2)-Thr(4)-N(delta)-propionyl-Orn(8)-Tyr(9)-NH2; D014316:Tritium; C076093:vasotocin, (beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-O-methyl-Tyr(2)-Thr(4)-Orn(8)-Tyr(9)-NH2; D014668:Vasotocin