Ghent University Academic Bibliography

Advanced

Analytical characterization of the BBB functionality of the opioid-peptides EM-1, EM-2 and CTAP.

Van Dorpe, Sylvia, Pintelon, Nathalie UGent, Adriaens, Antita, Polis, Ingeborgh UGent, Peremans, Kathelijne UGent, Pan, Weihong, Burvenich, Christian UGent and De Spiegeleer, Bart UGent (2009)
abstract
Peptides constitute a new group of promising drugs, with a diverse range of pharmacological activities [1]. One of their most promising targets is the Central Nervous System (CNS), where the Blood-Brain Barrier (BBB) constitutes an important flux-regulating compartment [2]. The development of selective and potent opioid peptide drugs for the major opioid receptor types (µ, δ and κ OR) continues to be a key objective in pharmacological research [3]. We present here the BBB influx and efflux data of the 3 µ-opioid peptides EM-1 (endomorphin-1), EM-2 (endomorphin-2) and CTAP (connective tissue activating peptide). Limited literature data indicate that both endomorphins are transported out of the brain by a saturable transport system[4], while CTAP can enter the brain from plasma [5]. However, no comprehensive data are available. The different steps are presented: - peptide handling and quality control by LC-DAD/MS, - chemical-metabolic stability, including the in-vitro metabolic study in standard mice tissues (i.e. plasma, brain, liver and kidney); - modification to its radiotracer and related QC; - BBB experiments: in-vivo BBB influx and efflux studies on mice. These studies are part of a global QSPR-project where the chromatographic properties of peptides are linked towards their BBB behavior. References: 1. Pan, W.H., et al., Effects of peptides: a cross-listing of peptides and their central actions published in the journal Peptides from 1994 through 1998. Peptides, 1999. 20(9): p. 1127-1138. 2. Kastin A.J., P.W., Peptide transport across the blood-brain barrier, in Peptide Transport and Delivery into the Central Nervous System, L.P.a.K. Prokai-Tatrai, Editor. 2003, Birkhäuser Verlag: Basel. p. 79-100. 3. Snyder, S.H. and G.W. Pasternak, Historical review: Opioid receptors. Trends in Pharmacological Sciences, 2003. 24(4): p. 198-205. 4. Kastin, A.J., et al., Saturable brain-to-blood transport of endomorphins. Experimental Brain Research, 2001. 139(1): p. 70-75. 5. Abbruscato, T.J., et al., Blood-brain barrier permeability and bioavailability of a highly potent and mu-selective opioid receptor antagonist, CTAP: Comparison with morphine. Journal of Pharmacology and Experimental Therapeutics, 1997. 280(1): p. 402-409.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
keyword
opioid, blood-brain barrier, peptides
conference start
2009-05-20
conference end
2009-05-20
language
English
UGent publication?
yes
classification
C3
copyright statement
I have retained and own the full copyright for this publication
id
670974
handle
http://hdl.handle.net/1854/LU-670974
date created
2009-05-28 15:55:28
date last changed
2016-12-19 15:36:45
@inproceedings{670974,
  abstract     = {Peptides constitute a new group of promising drugs, with a diverse range of pharmacological activities [1]. One of their most promising targets is the Central Nervous System (CNS), where the Blood-Brain Barrier (BBB) constitutes  an important flux-regulating compartment [2]. The development of selective and potent opioid peptide drugs for the major opioid receptor types ({\textmu}, \ensuremath{\delta} and \ensuremath{\kappa} OR) continues to be a key objective in pharmacological research [3].
We present here the BBB influx and efflux data of the 3 {\textmu}-opioid peptides EM-1 (endomorphin-1), EM-2 (endomorphin-2) and CTAP (connective tissue activating peptide). Limited literature data indicate that both endomorphins are transported out of the brain by a saturable transport system[4], while CTAP can enter the brain from plasma [5]. However, no comprehensive data are available.
The different steps are presented: 
-\unmatched{0009}peptide handling and quality control by LC-DAD/MS, 
-\unmatched{0009}chemical-metabolic stability, including the in-vitro metabolic study in standard mice tissues (i.e. plasma, brain, liver and kidney);
-\unmatched{0009}modification to its radiotracer and related QC; 
-\unmatched{0009}BBB experiments: in-vivo BBB influx and efflux studies on mice.
These studies are part of a global QSPR-project where the chromatographic properties of peptides are linked towards their BBB behavior.
References:
1.\unmatched{0009}Pan, W.H., et al., Effects of peptides: a cross-listing of peptides and their central actions published in the journal Peptides from 1994 through 1998. Peptides, 1999. 20(9): p. 1127-1138.
2.\unmatched{0009}Kastin A.J., P.W., Peptide transport across the blood-brain barrier, in Peptide Transport and Delivery into the Central Nervous System, L.P.a.K. Prokai-Tatrai, Editor. 2003, Birkh{\"a}user Verlag: Basel. p. 79-100.
3.\unmatched{0009}Snyder, S.H. and G.W. Pasternak, Historical review: Opioid receptors. Trends in Pharmacological Sciences, 2003. 24(4): p. 198-205.
4.\unmatched{0009}Kastin, A.J., et al., Saturable brain-to-blood transport of endomorphins. Experimental Brain Research, 2001. 139(1): p. 70-75.
5.\unmatched{0009}Abbruscato, T.J., et al., Blood-brain barrier permeability and bioavailability of a highly potent and mu-selective opioid receptor antagonist, CTAP: Comparison with morphine. Journal of Pharmacology and Experimental Therapeutics, 1997. 280(1): p. 402-409.},
  author       = {Van Dorpe, Sylvia and Pintelon, Nathalie and Adriaens, Antita and Polis, Ingeborgh and Peremans, Kathelijne and Pan, Weihong and Burvenich, Christian and De Spiegeleer, Bart},
  keyword      = {opioid,blood-brain barrier,peptides},
  language     = {eng},
  title        = {Analytical characterization of the BBB functionality of the opioid-peptides EM-1, EM-2 and CTAP.},
  year         = {2009},
}

Chicago
Van Dorpe, Sylvia, Nathalie Pintelon, Antita Adriaens, Ingeborgh Polis, Kathelijne Peremans, Weihong Pan, Christian Burvenich, and Bart De Spiegeleer. 2009. “Analytical Characterization of the BBB Functionality of the Opioid-peptides EM-1, EM-2 and CTAP.” In .
APA
Van Dorpe, S., Pintelon, N., Adriaens, A., Polis, I., Peremans, K., Pan, W., Burvenich, C., et al. (2009). Analytical characterization of the BBB functionality of the opioid-peptides EM-1, EM-2 and CTAP.
Vancouver
1.
Van Dorpe S, Pintelon N, Adriaens A, Polis I, Peremans K, Pan W, et al. Analytical characterization of the BBB functionality of the opioid-peptides EM-1, EM-2 and CTAP. 2009.
MLA
Van Dorpe, Sylvia, Nathalie Pintelon, Antita Adriaens, et al. “Analytical Characterization of the BBB Functionality of the Opioid-peptides EM-1, EM-2 and CTAP.” 2009. Print.