Regional variation in transport of pancreatic polypeptide across the blood-brain barrier of mice

Abstract

Blood-borne pancreatic polypeptide (PP) affects pancreatic secretion indirectly by acting through the central nervous system (CNS). PP, which is apparently not synthesized by brain, must cross the blood-brain barrier (BBB) to reach areas such as the cerebellum, an area rich in PP receptors, and to account for the PP found in cerebrospinal fluid (CSF). We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) into brain of intravenously injected radioiodinated PP (I-PP). The Ki was 1.15 (10(-3)) ml/g.min and was inhibited by unlabeled PP but not by tyrosine. HPLC showed that radioactivity in the brain was mostly intact I-PP. Up to 0.065% of the injected dose entered each gram of brain with preferential entry into the cerebellum and the pons-medulla. Capillary depletion confirmed that intact I-PP penetrated the BBB. I-PP exited the brain by a nonsaturable process. These results show that I-PP crosses the BBB by a saturable system to reach its receptors behind the BBB.