PT  - JOURNAL ARTICLE
AU  - Abba J. Kastin
AU  - Melita B. Fasold
AU  - James E. Zadina
TI  - Endomorphins, Met-Enkephalin, Tyr-MIF-1, and the P-glycoprotein Efflux System
AID  - 10.1124/dmd.30.3.231
DP  - 2002 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 231--234
VI  - 30
IP  - 3
4099  - http://dmd.aspetjournals.org/content/30/3/231.short
4100  - http://dmd.aspetjournals.org/content/30/3/231.full
SO  - Drug Metab Dispos2002 Mar 01; 30
AB  - The P-glycoprotein (P-gp) transport system, responsible for the efflux of many therapeutic drugs out of the brain, recently has been shown to transport the endogenous brain opiate endorphin. We used P-gp knockout mice (Mdr1a) and their controls to determine where P-gp is involved in the saturable efflux systems of four other endogenous opiate-modulating peptides across the blood-brain barrier (BBB). After injection of endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), Met-enkephalin (Tyr-Gly-Gly-Phe-Met-OH), and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) into the lateral ventricle of the mouse brain, residual radioactivity was measured at 0, 2, 5, 10, and 20 min later. The results showed no difference in the disappearance of any of these peptides from the brains of knockout mice compared with their controls. This demonstrates that unlike endorphin and morphine, P-gp does not seem to be required for the brain-to-blood transport of the endomorphins, Met-enkephalin, or Tyr-MIF-1 across the BBB. The American Society for Pharmacology and Experimental Therapeutics