FRACTIONATED-IRRADIATION ALTERS ENTERIC NEUROENDOCRINE PRODUCTS

Radiation profoundly alters the contractile activity of the small inte stine and colon. We hypothesized that some motor changes of the gut mi ght be secondary to impaired neural input to smooth muscle or abnormal release of gut endocrine peptides. The density of products within pep tidergic and cholinergic nerves and gut endocrine cells was estimated in six normal controls and six dogs who had received 1500 cGy in six e qual fractions of 250 cGy. Choline acetyltransferase, acetylcholineste rase, vasoactive intestinal peptide (VIP), substance P, peptide YY (PY Y), and motilin were measured in tissue specimens divided into mucosal -submucosal (MS) and muscularis externa (ME) layers. Tissue samples we re obtained from the duodenum, jejunum, ileum, and proximal and distal colon. In addition, serum levels of motilin and PYY were determined b efore and during the administration of 1500 cGy in four separate dogs instrumented to record upper gut contractile activity. Intrinsic choli nergic activity as estimated by choline acetyltransferase activity was unchanged, while acetylcholinesterase activity increased in the MS la yers of distal small bowel and colon. VIP was increased in the MS laye rs of jejunum and proximal colon as well as in the ME layers the jejun um and ileum. By contrast, substance P increased in the jejunal and pr oximal colonic MS layers and in the ME layers of the jejunum and ileum . Duodenal and jejunal motilin levels markedly decreased after radiati on exposure, while serum motilin levels continued to cycle at a decrea sed peak level with migrating motor complexes. Colonic PYY remained un changed but serum PYY levels decreased after irradiation. Increased ne uronal synthesis and inhibition of neurotransmitter release are potent ial explanations for elevated tissue concentrations of VIP, substance P, and acetylcholinesterase. There appeared to be differences in the s ensitivity of gut endocrine cells to irradiation. Changes in gut regul atory peptides and cholinergic enzyme activity occur with fractionated doses of abdominal irradiation, while the same schedule of irradiatio n produces striking changes in the canine small intestinal and colonic motor activity. It is therefore likely that alterations of contractil e events may be produced by changes in gut neuroendocrine products.