PERMEABILITY OF THE BLOOD-BRAIN-BARRIER TO THE NEUROTENSIN(8-13) ANALOG NT1

Neurotensin (NT) has been suggested to be a neuropeptide with therapeu tic potential. We used multiple-time regression analysis to measure th e unidirectional influx constant (K-i) of a tritiated analog of NT8-13 , NT1, with improved metabolic stability. The K-i of [H-3]NT1 across t he blood-brain barrier (BBB) was 5.12(10(-4)) ml/g-min and was decreas ed 66% by unlabeled NT1 system. The amount of NT1 crossing the BBB, 0. 087% of the injected dose per gram of brain, is consistent with its ex erting central effects after peripheral administration. The stable [H- 3]NT1 crossed the BBB in intact form as assessed by HPLC and completel y crossed the endothelial cells that comprise the BBB as assessed by t he capillary depletion method. The presence of a transport system coul d be important for the development of NT analogs.