ABSTRACT
The aim of the present study was to determine the effect of aspirin and indomethacin on epidermal growth factor (EGF) secretion in duodenal tissue fragments cultivated in vitro. The fragments were obtained from healthy subjects by gastroscopy, cultured in McCoy's medium and gassed with 95% O2 and 5% CO2 at 37 degrees C. After an incubation of 30 min, the culture medium was decanted, and the quantity of hormone determined by radioimmunoassay. The mean EGF level detected in the medium was 10.94 ng/mg protein tissue. The addition of aspirin (final concentration 10(-7) M) to the medium reduced mean EGF levels to 7.5 ng/mg (p less than 0.05), whereas aspirin 10(-8) M did not produce such a modification. The addition of indomethacin (final concentration 10(-8) M) decreased mean EGF levels to 5.37 ng/mg (p less than 0.001). In all experimental conditions, the addition of anti-somatostatin (SRIF) antibodies determined a remarkable increase in EGF (p less than 0.01). The results of this study show aspirin and indomethacin to be direct, not SRIF-mediated inhibitors of EGF release.
Subject(s)
Aspirin/pharmacology , Duodenum/drug effects , Epidermal Growth Factor/metabolism , Indomethacin/pharmacology , Adult , Cells, Cultured , Duodenum/metabolism , Female , Humans , Male , Middle Aged , Radioimmunoassay , Somatostatin/physiologyABSTRACT
Duodenal biopsies obtained from seven normal subjects and six ulcerous patients were cultured in vitro for 30 min at 37 degrees C under various experimental conditions. Epidermal growth factor (EGF) and somatostatin released in the culture medium were determined by radioimmunoassay. Under basal conditions, EGF and somatostatin levels were significantly higher in normal subjects (11.49 +/- 3.07 ng/mg protein and 3.06 +/- 0.8 ng/mg protein, respectively) than in ulcerous patients (6.9 +/- 1.98 ng/mg protein and 1.75 +/- 1.23 ng/mg protein, respectively). However, when antibodies to somatostatin and vasoactive intestinal polypeptide (VIP) were added together to the culture media, in ulcerous patients, EGF levels also were lower as absolute values, but were higher as a percentage of variation than controls (p less than 0.05). The fall of EGF secretion from tissue cultures of ulcerous patients could be the consequence of endocrine cellular loss or damage, rather than the cause of ulceration. Moreover, the EGF-producing cells around the lesion in ulcerous patients seems to be hyperactive, and this hyperfunction of EGF-producing cells might contribute to the in vivo repair of tissue damage.
Subject(s)
Epidermal Growth Factor/physiology , Intestinal Mucosa/metabolism , Peptic Ulcer/physiopathology , Adult , Antibodies/pharmacology , Biopsy , Culture Techniques , Epidermal Growth Factor/metabolism , Female , Humans , Male , Middle Aged , Radioimmunoassay , Somatostatin/immunology , Somatostatin/metabolism , Vasoactive Intestinal Peptide/pharmacologyABSTRACT
Epidermal Growth Factor (EGF)-containing cells have been found in Brunner's glands in the same area where several regulatory peptides are released. The present study was aimed at testing the release and the regulation of EGF secretion from cultured duodenal biopsies obtained from healthy individuals by gastroscopy. The effects and the interaction of VIP and somatostatin on the hormone release were studied. Duodenal biopsies were cultured at 37 degrees C in Mc Coy's buffer, gassed with 95% O2 and 5% CO2. After 30 min, the culture medium was decanted for the measurement of the hormones by RIA. To measure the protein content, the tissue was then homogenized; EGF detected in the culture was 11.5 ng/mg protein. The addition of VIP in the medium increased EGF mean levels to 21.6 ng/mg protein (P less than 0.01). The biopsies thus obtained were cultured with anti-somatostatin antibodies to evaluate the influence of endogenous somatostatin on EGF secretion. The inclusion of anti-somatostatin antibodies increased the EGF levels to 41.2 ng/mg protein (P less than 0.01). The combined addition of anti-somatostatin antibodies and VIP in the culture caused a mean EGF increase significantly higher than the values obtained separately by VIP and somatostatin (P less than 0.01). In conclusion, we can suggest a triangular interaction model of EGF release, where the somatostatin seems to be the negative monitor of over-secreted VIP and EGF from the gut.
