beta-Endorphin: stability, clearance behavior, and entry into the central nervous system after intravenous injection of the tritiated peptide in rats and rabbits.

Abstract

Rabbits and rats were given i.v. injections of [3H] human .beta.-endorphin. The levels of .beta.-endorphin were followed by the decrease in radioactivity in the plasma of rats or rabbits, and by the increase in radioactivity in the CSF of the rabbit. The results were identical with the [3H] label on either tyrosine-1 or -27. The plasma distribution times were 2 and 5 min in the rat and rabbit, respectively, with a later clearance time of .apprx. 1-8 h. In the rat, .apprx. 50% of the radioactivity in the plasma was intact human .beta.-endorphin, 45 min after injection. Radioactivity appeared in the CSF of the rabbit within 30 s after injection and reached a plateau in .apprx. 60-90 min after injection. Approximately 75% of the radioactivity in the CSF of the rabbit was intact human .beta.-endorphin. In the brain hemispheres of the rat and the rabbit, the only significant radiolabeled product was radioactive tyrosine. Rat plasma levels of .beta.-endorphin decreased dramatically after hypophysectomy, which only slightly lowered the levels in the brain. .beta.-Endorphin, upon entry into the plasma, is either not significantly taken up into the brain, or is broken down with extreme rapidity upon entry into the brain, although it apparently does enter the CSF.