Peptide and peptide analog transport systems at the blood-CSF barrier.
In addition to being the main source of cerebrospinal fluid (CSF) secretion, the choroid plexuses are involved in the supply and distribution of peptides to brain, the removal of toxic metabolites, the excretion of xenobiotics, and the delivery of drugs as an alternative route to the blood-brain barrier (BBB). The discovery of proton-coupled oligopeptide transporters in choroid plexus has generated considerable interest regarding their physiologic role at the blood-cerebrospinal fluid interface and their potential for peptide/antagonist pharmacotherapy in the central nervous system. Many of the same factors that affect the disposition of naturally occurring peptides in brain will also affect the disposition of exogenously delivered peptide or peptidomimetic drugs. Therefore, this review addresses three main areas: (1) choroid plexus structure, physiology, and barrier function in relation to peptide transport; (2) polypeptide transport and secretion mechanisms into cerebrospinal fluid; and (3) molecular physiology, expression, and functional activity of proton-coupled oligopeptide transporters in choroid plexus.
Smith
David E
DE
Department of Pharmaceutical Sciences, College of Pharmacy and Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, MI 48109, USA. smithb@umich.edu
Johanson
Conrad E
CE
Keep
Richard F
RF
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*
D026901:Membrane Transport Proteins; D010455:Peptides; C043912:peptide permease