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

• Published in: Pharmacology, biochemistry and behavior Vol. 51; no. 1; pp. 139 - 147
• Main Authors: Banks, William A., Kastin, Abba J., Jaspan, Jonathan B.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-1995; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier; Brain - anatomy & histology; Brain - metabolism; Brain-gut axis; Cerebellum; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrospinal fluid; Chromatography, High Pressure Liquid; Fundamental and applied biological sciences. Psychology; Male; Mice; Mice, Inbred ICR; Pancreas; Pancreatic Polypeptide - chemistry; Pancreatic Polypeptide - pharmacokinetics; Regression Analysis; Solubility; Tyrosine - pharmacokinetics; Vertebrates: nervous system and sense organs; Cerebellum; Cerebrospinal fluid; Pancreas; Brain-gut axis; Pancreatic hormone; Vertebrata; Mammalia; Pancreatic polypeptide; Penetration; Intravenous administration; Mouse; Peptide hormone; Rodentia; Blood brain barrier; Brain (vertebrata)
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(94)00412-C

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 (
K
i
) into brain of intravenously injected radioiodinated PP (I-PP). The
K
i
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.