A substance P receptor antagonist (FK 888) modifies gut alterations induced by ionizing radiation

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Abstract
Purpose: We previously reported disturbances of ileal substance P (SP) levels and of characteristics of specific receptors after ionizing radiation associated with disorders of intestinal motility. The aim of this study was to investigate the effect of a SP receptor blockade by FK 888 on gut SP levels and contractile properties after rat irradiation. Materials and methods: Rats were exposed to 6 Gy whole-body gamma irradiation and injected 1 h post-irradiation with FK 888 for 3 days (0.1mg/kg/day). Plasma and ileal SP concentrations, ileal muscle SP receptor binding and SP-induced contractions in isolated ileum were investigated 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 receptor characteristics in irradiated animals. In contrast, FK 888 treatment 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 treatment decreased efficacy of ileal contraction in both the control and irradiated rat but surprisingly it increased potency at day 3 and decreased it at day 14 in the irradiated rat. Conclusions: The findings demonstrate that a SP receptor antagonist could be effective on intestine contractility alteration induced several days after ionizing radiation exposure but not at 3 days after irradiation.

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