INTESTINAL-ABSORPTION OF STABLE CYCLIC GLYCYLPHENYLALANINE - COMPARISON WITH THE LINEAR FORM

The absorption, especially the stability and transportability, of the cyclic peptide cyclic glycylphenylalanine (cyclo(Gly-Phe)) and the lin ear peptides glycylphenylalanine, glycyl-D-phenylalanine and phenylala nylglycine have been studied in rat small intestine. Linear peptides w ere degraded on the mucosal side and only glycyl-D-phenylalanine appea red on the serosal side. However, cyclo(Gly-Phe) was stable on the muc osal side and appeared on the serosal side. Furthermore, the absorptio n clearance of cyclo(Gly-Phe) was higher than that of glycyl-D-phenyla lanine. in the presence of the peptidase inhibitor bestatin, the degra dation of linear peptides was reduced and linear peptides appeared on the serosal side, but only phenylalanylglycine, which is transported b y the oligopeptide transporter, was absorbed faster than cyclo(Gly-Phe ). The absorption clearance of cyclo(Gly-Phe) was reduced as its conce ntration was increased from 125 mu M to 500 mu M. Furthermore, the abs orption clearance of cyclo(Gly-Phe) at 125 mu M was reduced at 4 degre es C or in the presence of glycylsarcosine and cephalexin, which are t ransported by the oligopeptide transporter. These results indicated th at cyclo(Gly-Phe) was stable enough to be absorbed and was transported in part by the oligopeptide transporter rather than completely by pas sive diffusion.