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Am J Physiol Gastrointest Liver Physiol (January 9, 2002). doi:10.1152/ajpgi.00457.2001
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Articles in PresS, published online ahead of print January 9, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00457.2001
Submitted on October 25, 2001
Accepted on December 22, 2001

Alterations of the VIP-stimulated cAMP pathway in rat distal colon following abdominal irradiation

Eric Morel1, Isabelle Dublineau1, Fabienne Lebrun1, and Nina M Griffiths1*

1 DPHD/SARAM, IPSN, Fontenay-aux Roses Cedex, 92265, France

* To whom correspondence should be addressed. E-mail: nina.griffiths{at}ipsn.fr.

Ionizing radiation induces hyporesponsiveness of rat colonic mucosa to VIP (Vasoactive Intestinal Peptide). Possible mechanisms responsible for this hyporesponsiveness of the cAMP communication pathway in rat colon were investigated. VIP- and forskolin- stimulated Isc responses were studied following 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 four days after irradiation (decrease of 80%). Cyclic AMP analogue-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 to these functional alteration. 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 decrease of crypt cell number.




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