Opiate-modulating tetrapeptides such as tyrosine-melanocyte-stimulating hor
mone-release inhibiting factor-1 (Tyr-MIF-1; Sr-Pro-Leu-Gly-NH,) and Tyr-W-
MIF-1 (Tyr-Pro-Trp-Gly-NH2) are saturably transported From brain to blood.
We examined whether two recently described endogenous opiate tetrapeptides
with similar structures, the mu-specific endomorphins, also are transported
across the blood-brain barrier (BBB). We found that the efflux rates of en
domorphin-1 (Sr-Pro-Trp-PheNH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) w
ere each self-inhibited by an excess of the respective endomorphin, thereby
defining saturable transport. Cross-inhibition of the transport of each en
domorphin by the other indicated shared transport. By contrast, no inhibiti
on of the efflux of either endomorphin resulted from coadministration of Ty
r-MIF-1, indicating that peptide transport system-1 (PTS-1) was not involve
d. Tyr-W-MIF-1, which is partially transported by PTS-1, significantly (P<0
.01) decreased the transport of endomorphin-1 and tended (P=0.051) to decre
ase the transport of endomorphin-2. consistent with its role as both an opi
ate and antiopiate. Although involved in modulation of pain, coinjection of
calcitonin gene-related peptide or constriction of the sciatic nerve did n
ot appear to inhibit endomorphin efflux. Thus, the results demonstrate the
existence of a new efflux system across the BBB which saturably transports
endomorphins from brain to blood.