Alterations of the VIP-stimulated cAMP pathway in rat distal colon after abdominal irradiation.
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 (I(sc)) 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 I(sc) 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.
Morel
E
E
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.
Dublineau
I
I
Lebrun
F
F
Griffiths
N M
NM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000378:metabolism* / Q000528:radiation effects*; D000242:Cyclic AMP / Q000378:metabolism*; D015194:Diffusion Chambers, Culture; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008297:Male; D011485:Protein Binding / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002712:Chlorides; D005765:Gastrointestinal Agents; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D003994:Bucladesine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases