title: Response of the antral mucosa of the rat stomach to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) produces a striking hypergastrinemia in rats that is thought to mediate the antiatrophy effect of TCDD on the oxyntic gland mucosa of the stomach. However, effects of TCDD on the antral mucosa, which is the origin of most physiologically released gastrin and is not a target for the trophic action of gastrin, has yet to be thoroughly investigated. Also gastrin release from gastrin-containing cells (i.e., G-cells) in the antral mucosa is inhibited by the paracrine secretion of somatostatin from D-cells in the antrum. Our purpose was to determine if the antral mucosa is affected by the trophic influence of TCDD and if alterations in antral mucosa levels of gastrin or somatostatin cause the hypergastrinemia. TCDD (100 micrograms/kg, Day 14 post-treatment) had a trophic effect on the antral mucosa. This was demonstrated histologically and by significant increases in antral wet weight and antral mucosa height. In contrast, pair-fed control rats that lost the same amount of body weight developed antral mucosa atrophy. With respect to serum and antral levels of gastrointestinal hormones, TCDD produced a 7- to 10-fold increase in serum gastrin concentrations that was not detected until Day 14 post-treatment. In contrast, serum gastrin concentrations in pair-fed control rats were comparable to those of control rats. The number of G-cells in the antral mucosa was not affected by either TCDD treatment or paired-feed restriction. These findings demonstrate that hypergastrinemia in TCDD-treated rats is not caused by reduced feed intake or antral G-cell hyperplasia. A major finding was that antral mucosa levels of both gastrin and somatostatin were decreased significantly in TCDD-treated rats. However, the temporal development and dose-dependence of these TCDD effects on antral hormone levels were quite different than those for hypergastrinemia. TCDD-induced decreases in antral levels of gastrin and somatostatin were detected 1 week earlier than hypergastrinemia. Also, the ED50 of TCDD on Day 14 post-treatment for the decrease in antral mucosa content and concentration of gastrin (29 and 22 micrograms/kg, respectively) and somatostatin (24 and 19 micrograms/kg, respectively) was less than that for hypergastrinemia (46 micrograms/kg). These time- and dose-dependent differences demonstrate that hypergastrinemia in TCDD-treated rats is not a consequence of reduced antral levels of gastrin or somatostatin. We conclude that the antral mucosa, an epithelial tissue not responsive to the proliferative effect of gastrin, is nevertheless a target for the trophic influence and gastrointestinal hormone-altering effects of TCDD.
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison 53706.
authors.forename: H M
authors.initials: HM
authors.lastname: Theobald
authors.forename: G B
authors.initials: GB
authors.lastname: Ingall
authors.forename: T A
authors.initials: TA
authors.lastname: Mably
authors.forename: R E
authors.initials: RE
authors.lastname: Peterson
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D005755:Gastrins / Q000032:analysis / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011506:Proteins / Q000032:analysis; D011706:Pyloric Antrum; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000032:analysis; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D005755:Gastrins; D000072317:Polychlorinated Dibenzodioxins; D011506:Proteins; D013004:Somatostatin