Saturable brain-to-blood transport of endomorphins

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.