REGIONAL DIFFERENCES IN GASTROINTESTINAL PROCESSING AND ABSORPTION OF EPIDERMAL GROWTH-FACTOR IN SUCKLING RATS

Gastrointestinal processing and absorption in vivo of I-125-labeled epidermal growth factor (I-125-EGF) was studied in isolated stomach, jejunum, and ileum of 12-day-old suckling rats. Dose dependency and regional differences in the processing and absorption of EGF were determined. At 60 min after administration of I-125-EGF into the isolated gastric lumen, > 90% of radioactive material was recovered from gastric wall and lumen in both suckling and weanling rats. On the other hand, a considerable amount of EGF was absorbed (in immunoreactive and receptor active form) from isolated jejunum and ileum of suckling rats. The absorption of EGF from isolated jejunum and ileum increased linearly with the dose of EGF administered up to 1-mu-g/rat; absorption of orogastrically administered EGF was also increased linearly with the dose of EGF administered (up to 5-mu-g/rat). Reverse-phase high-performance liquid chromatographic analysis of tissue extracts demonstrated that I-125-EGF is stable in gastric lumen but only partially stable in the jejunal lumen. Carboxy-terminally processed forms of EGF were detected in the luminal flushings of jejunum and ileum and in the wall of the stomach, jejunum, and ileum. I-125-des(48-53)EGF was found in ileal flushings and in the walls of the stomach, jejunum, and ileum, whereas I-125-des(53)EGF and I-125-des(49-53)EGF were detected in jejunal flushings. Receptor binding of I-125-des(53)EGF was significantly greater (by 57%) than that of intact I-125-EGF, but receptor binding of I-125-des(49-53)EGF and I-125-des(48-53)EGF was greatly diminished by 57 and 86%, respectively. These studies demonstrate the existence of a high capacity and regional differences in the gastrointestinal absorption of EGF. Furthermore, EGF undergoes carboxy-terminal processing in the gastrointestinal tract during its absorption.