@article {Banks1062, author = {William A. Banks and Martin Goulet and James R. Rusche and Michael L. Niehoff and Richard Boismenu}, title = {Differential Transport of a Secretin Analog across the Blood-Brain and Blood-Cerebrospinal Fluid Barriers of the Mouse}, volume = {302}, number = {3}, pages = {1062--1069}, year = {2002}, doi = {10.1124/jpet.102.036129}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Secretin is a gastrointestinal peptide belonging to the vasoactive intestinal peptide (VIP)/glucagon/pituitary adenylate cyclase-activating polypeptide (PACAP) family recently suggested to have therapeutic effects in autism. A direct effect on brain would require secretin to cross the blood-brain barrier (BBB), an ability other members of the VIP/PACAP family have. Herein, we examined whether a secretin analog (SA) radioactively labeled with 131I (I-SA) could cross the BBB of 4-week-old mice. We found I-SA was rapidly cleared from serum with fragments not precipitating with acid appearing in brain and serum. Levels of radioactivity were corrected to reflect only intact I-SA as estimated by acid precipitation. After i.v. injection, I-SA was taken up by brain at a modest rate of 0.9 to 1.5 μl/g-mm. Capillary depletion, brain perfusion, and high-performance liquid chromatography were used to confirm the passage of intact I-SA across the BBB. I-SA entered every brain region, with the highest uptake into the hypothalamus and cerebrospinal fluid (CSF). Unlabeled SA (10 μg/mouse) did not inhibit uptake by brain but did inhibit clearance from blood and uptake by the CSF, colon, kidney, and liver. The decreased clearance of I-SA from blood increased the percentage of the i.v. injected dose taken up per brain (\%Inj/g) from about 0.118 to 0.295\%Inj/g. In conclusion, SA crosses the vascular barrier by a nonsaturable process and the choroid plexus by a saturable process in amounts that for other members of its family produce central nervous system (CNS) effects. This passage provides a pathway through which peripherally administered SA could affect the CNS. U.S. Government}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/302/3/1062}, eprint = {https://jpet.aspetjournals.org/content/302/3/1062.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }