Intestinal absorption mechanisms of thyrotropin-releasing hormone.

Intestinal absorption mechanisms of thyrotropin-releasing hormone (TRH) following the oral administration of TRH-tartrate (TRH-T) were studied in animals. When TRH-T was orally administered to rats or beagle-dogs, absorption of TRH showed apparent saturation and decreased with food ingestion. TRH is very stable against gastrointestinal digestive enzymes, homogenized intestine and epithelial cells. First pass effect in the liver was not observed in beagle-dogs. Absorption site specificity was found in rats, namely TRH can be absorbed from only the upper part of the small intestine. A saturation phenomenon was also observed in in situ and everted sac experiments. TRH absorption was inhibited by the existence of oligopeptides and some beta-lactam antibiotics that had been reported to be absorbed by active transport or carrier-mediated transport systems. The transfer of TRH from mucosal to serosal solutions was inhibited by the replacement of medium Na ions by K ions and by the existence of oligopeptides. The transfer rate from serosal side to mucosal side was much slower than that from mucosal side to serosal side. These results suggested that there should be a certain carrier-mediated transport system in the absorption process of TRH.