Abstract: |
Interactions between the brain and the body are complex. While the peripheral nervous system provides important pathways for communication, evidence now indicates that the brain is capable of releasing important peripherally acting neurochemicals. Intracerebroventricular (i.c.v.) administration of 125I-(D-Pen2,D-Pen5)enkephalin, 125I-beta-endorphin or 125I-Morphine leads to their rapid appearance in blood. The transport system is saturable, with the efflux of 125I-beta-endorphin and 125I-Morphine competed by beta-endorphin and morphine, respectively, in a dose-dependent manner. Immunohistochemically, high levels of Pgp1 were observed in the choroid plexus. Antisense oligodeoxynucleotides downregulating Pgp1, dramatically reduced the efflux of iodinated compounds from the brain to the circulation and altered the analgesic activity of beta-endorphin and morphine. These findings demonstrate: 1) the brain's ability to secrete compounds to the periphery via the Pgp1 transporter, illustrating a potentially important mind/body communication pathway and 2) the Pgp1 transporter's role in the production of beta-endorphin and morphine analgesia. |