PMID- 8584471
OWN - NLM
STAT- MEDLINE
DCOM- 19960315
LR  - 20190818
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 12
IP  - 10
DP  - 1995 Oct
TI  - Cerebrovascular permeability to peptides: manipulations of transport systems at 
      the blood-brain barrier.
PG  - 1395-406
AB  - The study of peptide transport across the blood-brain barrier (BBB) is a field 
      fraught with conflicting interpretations. This review presents a fairly strong 
      case that peptides can be differentially transported at the BBB. However, minimal 
      transport of peptides could have important impact on central nervous system (CNS) 
      functions since only small amounts are needed for physiologic pharmacologic 
      and/or pathologic effects. Several BBB peptide transport mechanisms (i.e., 
      receptor-mediated, absorptive-mediated, carrier-mediated and non-specific passive 
      diffusion), as well as non-transport processes (i.e., endocytosis without 
      transcytosis, absorption and metabolism) are discussed. It is emphasized that 
      peptide transport systems at the BBB could be important targets for both 
      therapeutic delivery of peptides and the development of certain brain 
      pathologies. Strategies to manipulate peptide BBB transport processes have been 
      discussed including lipidization, chemical modifications of the N-terminal end, 
      coupling of transport with post-BBB metabolism and formation of potent 
      neuroactive peptides, up-regulation of putative peptide transporters, use of 
      chimeric peptides in which non-transportable peptide is chemically linked to a 
      transportable peptide, use of monoclonal antibodies against peptide receptors, 
      and binding of circulating peptides to apolipoproteins. It is suggested that 
      future directions should be directed towards development of molecular strategies 
      to up-regulate specific BBB peptide transporters to enhance brain delivery of 
      peptide neuropharmaceuticals, or to down-regulate transport of peptides with 
      potential role in cerebral pathogenesis.
FAU - Zlokovic, B V
AU  - Zlokovic BV
AD  - Department of Neurological Surgery, Children's Hospital Los Angeles, University 
      of Southern California School of Medicine 90033, USA.
LA  - eng
GR  - AG08051/AG/NIA NIH HHS/United States
GR  - EY 09399/EY/NEI NIH HHS/United States
GR  - NS31945/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Peptides)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - *Blood-Brain Barrier
MH  - *Capillary Permeability
MH  - *Cerebrovascular Circulation
MH  - Glutathione/metabolism
MH  - Peptides/chemistry/*pharmacokinetics
RF  - 72
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - 10.1023/a:1016254514167 [doi]
PST - ppublish
SO  - Pharm Res. 1995 Oct;12(10):1395-406. doi: 10.1023/a:1016254514167.