Vol. 282, Issue 5, G835-G843, May 2002
Alterations of the VIP-stimulated cAMP pathway in rat distal
colon after abdominal irradiation
E.
Morel,
I.
Dublineau,
F.
Lebrun, and
N. M.
Griffiths
Institut de Protection et de Sûreté Nucléaire,
Département de Protection et de la santé de l'Homme et
de Dosimétrie, Section Autonome de Radiobiologie
Appliquée à la Médecine, F-92265 Fontenay-aux-Roses
Cedex, France
Ionizing radiation induces
hyporesponsiveness of rat colonic mucosa to vasoactive intestinal
peptide (VIP). Possible mechanisms responsible for this
hyporesponsiveness of the cAMP communication pathway in rat colon were
investigated. VIP- and forskolin-stimulated short-circuit current
(Isc) responses were studied after a 10-Gy abdominal irradiation in Ussing chambers as well as in single, isolated
crypts. Adenylyl cyclase (AC) activity and VIP receptor characteristics
were determined in mucosal membrane preparations. In addition,
alterations in crypt morphology were studied. Impaired secretory
responses to VIP and forskolin were observed 4 days after irradiation
(decrease of 80%). cAMP analog-stimulated Isc responses were unchanged. In isolated crypts, VIP- and
forskolin-stimulated cAMP accumulation was markedly reduced by 80 and
50%, respectively. VIP-stimulated AC activity and VIP receptor number
were decreased in membrane preparations. No major change of cellularity
was associated with these functional alterations. In conclusion, the
decreased secretory responses to VIP of rat colon are associated with
reduced cAMP accumulation, decreased AC activity, and diminution of VIP receptor numbers without a marked decrease of crypt cell number.
colonic crypts; radiation; hyporesponsiveness; adenylyl cyclase; short-circuit current
