Persistence of modifications in 5-HT-associated short circuit current responses in rat distal colon following radiation exposure
A. Ropenga and N. M. Griffiths
PHYSOCS , Oxford (GB), 19-21/03/2001
Previous work has shown modifications in fluid and electrolyte transport in rat colon following exposure to ionising radiation. In particular, during the first few days following exposure neurally-evoked and 5-hydroxytryptamine (5-HT) short circuit current (Isc) responses are attenuated (François et al, 2000). Moreover the novel appearance at 7 days of a response associated with 5-HT4 receptors after Electrical Field Stimulation (EFS) was established. The aim of the experiments was to study the persistency of late post irradiation modifications with particular interest in 5-HT4 receptors.
Anaesthetized ( isofurane inhalation ) rats ( Wistar ) were exposed to a non lethal inferior hemi body irradiation of 10 Gy (X rays). At 3, 7, 14, 28, 43 and 92 days post exposure the distal colon was removed from euthanised animals (overdose sodium pentobarbitone, 100 mg/kg; i.p.) and mounted in Ussing chambers for measurements of short circuit current (Isc) in basal and stimulated conditions. Each stimulation was performed on stripped (removal of external muscle layers and myenteric plexus) and non-stripped preparations. The tissue was stimulated by exogenous addition of 5-HT (10-5 M) or by EFS Field (3s stimulation time, frequency 35 Hz). All experiments were conduced according to the French regulations for animal experimentation (Ministry of Agriculture Act No.87848, October 19, 1987).
At 3 and 7 days post irradiation in stripped tissues basal Isc was increased, whereas in non stripped tissues basal Isc tended to be decreased. Following the addition of exogenous 5-HT on stripped tissue, Isc responses were attenuated at 3 days with a tendency for reduced responses up to 28 days. Concomitant with these changes in basal and 5-HT-stimulated Isc responses at 3 days, EFS responses were also decreased in both tissue preparations. In control tissues, EFS responses were unchanged in the presence of the 5-HT4-receptor antagonist (SB 204070, 10-7 M ) whereas 5-HT-stimulated Isc responses were markedly reduced. In contrast, after irradiation SB 204070 attenuated EFS-induced Isc responses between 7 (-50%) and 43 (-35%) days post irradiation. These results provide evidence that after 10 Gy hemi body irradiation modifications persist more than 7 days post exposure. In particular, they seem to involve not only epithelial 5-HT4 receptors but also neural modifications.