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

Sylvia Van Dorpe UGent, Nathalie Pintelon UGent, Antita Adriaens UGent, Ingeborgh Polis UGent, Kathelijne Peremans UGent, Weihong Pan, Christian Burvenich UGent and Bart De Spiegeleer 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
2009-06-05 09:58:42
@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.