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


METHODS
Rats were exposed to 6 Gy whole-body gamma-irradiation and injected 1 h post-irradiation with FK 888 for 3 days (0.1 mg/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.
Esposito
V
V
Institut de Protection et de Sûreté Nucléaire, Département de Protection de la santé de l'Homme et de Dosimétrie, IPSN, Fontenay-aux-Roses, France.
Linard
C
C
Wysocki
J
J
Griffiths
N M
NM
Mathe
D
D
D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D007211:Indoles / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000528:radiation effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000097:blood / Q000378:metabolism*
D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; C078949:FK 888; D013373:Substance P