SEROTONIN AND NEUROENDOCRINE PEPTIDES INFLUENCE DNA-SYNTHESIS IN RAT AND HUMAN SMALL-INTESTINAL CELLS IN-VITRO

Animal studies suggest a mediator role for neuroendocrine peptides and amines in regulating cell proliferation in the gastrointestinal epith elium. Our aim was to examine the effect oi serotonin and selected gas trointestinal peptides on DNA synthesis in a rat and human small intes tinal cell line in vitro. IEC-6 and FHs-74 cells were incubated with e pidermal growth factor (EGF), insulin-like growth factor II, glucagon, substance P, neurokinin A, calcitonin gene-related peptide (GRP, CCGR P), neurotensin and serotonin. The cells were labelled with [methyl-H- 3] thymidine and processed for autoradiography. DNA synthesis was eval uated by the labelling index. Epidermal growth factor, insulin-like gr owth factor II, glucagon, and substance P increased the labelling inde x in a dose-related manner (P < 0.003). In contrast, a significant dos e-dependent reduction of the labelling index was observed after admini stration of serotonin and neurokinin A (P < 0.0001). Neurotensin and C GRP did not affect the labelling index. EGF, insulin-like growth facto r II, glucagon, substance P, serotonin and neurokinin A may be importa nt physiological regulators of proliferation, of gastrointestinal cell s.