A SUBSTANCE-P RECEPTOR ANTAGONIST (FK-888) MODIFIES GUT ALTERATIONS INDUCED BY IONIZING-RADIATION

Purpose: We previously reported disturbances of ileal substance P (SP) levels and of characteristics of specific receptors after ionizing ra diation associated with disorders of intestinal motility. The aim of t his study was to investigate the effect of a SP receptor blockade by F K 888 on gut SP levels and contractile properties after rat irradiatio n. Materials and methods: Rats were exposed to 6 Gy whole-body gamma-i rradiation and injected Ih post-irradiation with FK 888 for 3 days (0. 1 mg/kg/day). Plasma and ileal. SP concentrations, ileal muscle SP rec eptor binding and SP-induced contractions in isolated ileum were inves tigated 3 and 14 days post-irradiation and FK 888 treatment. Results: Irradiation induced an increase of total SP binding site number at day 3 (1.3-fold) and day 14 (1.6-fold). FK 888 had no effect on SP recept or characteristics in irradiated animals. In contrast, FK 888 treatmen t caused a reduction of endogenous ileal SP level in mucosal(-29%) and muscularis (-40%) layers at day 3 and these decreases were greater at day 14, -88% in mucosal and -61% in muscularis layers. FK 888 treatme nt decreased efficacy of ileal contraction in both the control and irr adiated rat but surprisingly it increased potency at day 3 and decreas ed it at day 14 in the irradiated rat. Conclusions: The findings demon strate that a SP receptor antagonist could be effective on intestine c ontractility alteration induced several days after ionizing radiation exposure but not at 3 days after irradiation.