PT  - JOURNAL ARTICLE
AU  - Sarah A. Thomas
AU  - Thomas J. Abbruscato
AU  - Victor J. Hruby
AU  - Thomas P. Davis
TI  - The Entry of [<span class="sc">d</span>-Penicillamine<sup>2,5</sup>]Enkephalin into the Central Nervous System: Saturation Kinetics and Specificity
DP  - 1997 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1235--1240
VI  - 280
IP  - 3
4099  - http://jpet.aspetjournals.org/content/280/3/1235.short
4100  - http://jpet.aspetjournals.org/content/280/3/1235.full
SO  - J Pharmacol Exp Ther1997 Mar 01; 280
AB  - The delta opioid receptor-selective, enzymatically stable peptide [d-Penicillamine2,5]enkephalin (DPDPE) has recently acquired special significance with the identification of a saturable uptake system for this analgesic into the CNS. The aim of the present study was to characterize further the entry of [3H]DPDPE into the brain and CSF by means of a bilateralin situ brain perfusion method. Initial experiments revealed a saturable [3H]DPDPE uptake into the brain that followed Michaelis-Menten type kinetics with a K m value of 45.5 ± 27.6 μM, a V max value of 51.1 ± 13.2 pmol · min−1 · g−1 and a K d value of 0.6 ± 0.3 μl · min−1 · g−1. Uptake of [3H]DPDPE into the CSF could not be inhibited (K d = 0.9 ± 0.1 μl · min−1 · g−1). Entry of [3H]DPDPE into the CNS was not inhibited in the presence of 10 mM 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid (BCH) or 50 μM ICI 174,864, which suggests that the saturable mechanism does not involve the large neutral amino acid transporter or binding to opioid receptors. It would also appear that [3H]DPDPE is not in competition with either poly-l-lysine or insulin to enter the CNS. However, both of these substances significantly increased the CNS entry of [3H]DPDPE but not that of the vascular space marker [14C]sucrose, and this may have valuable clinical implications. It is not known at present which saturable uptake mechanism is responsible for the CNS entry of [3H]DPDPE, but overall the results suggest a carrier-mediated transport system. The American Society for Pharmacology and Experimental Therapeutics