Intestinal adaptation in atrophic rat ileum is accompanied by supersensitivity to vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide and nitric oxide.
BACKGROUND
Intestinal inactivity leads to atrophic changes and concomitant alterations in the expression of neurotransmitters in the enteric nervous system. In atrophic rat ileum neurones expressing vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) decrease in number while nitric oxide synthase (NOS) expressing neurones increase. Since little is known about functional changes accompanying intestinal atrophy the aim of the present study was to investigate relaxatory responses to VIP, PACAP-27 and nitric oxide (NO) in longitudinal smooth muscle from atrophic rat ileum.


METHODS
To create a dysfunctional (atrophic) intestine, the distal 10 cm of rat ileum was surgically bypassed. In vitro experiments were carried out on longitudinal muscle strips from rat ileum having been sham-operated, one week or four weeks bypassed.


RESULTS
The amplitudes of the relaxatory responses to PACAP-27, VIP and the NO-donor S-nitroso-N-acetylpenicillamine (SNAP), but not forskolin, were significantly increased in the one-week bypassed ileum. In the four-weeks bypassed ileum the VIP, PACAP-27, SNAP and forskolin evoked relaxations were of the same magnitude as those of the sham-operated. The augmented responses to both VIP and PACAP-27 could be blocked by pre-treatment with apamin while N(G)-nitro-L-arginine methyl ester (L-NAME) and tetrodotoxin were ineffective. In contrast to sham-operated and four-weeks bypassed ileum, cross-desensitization between VIP and PACAP-27 was noted after one week of bypass.


CONCLUSIONS
Intestinal adaptation after bypassing the distal ileum of the rat includes a transient supersensitivity of the longitudinal muscle to the NO donor SNAP, VIP and PACAP-27. These augmented relaxatory responses may contribute to the hypomotility noted in inactive intestine.
Ekelund
M
M
Dept. of Physiological Sciences, Lund University Hospital, Sweden.
Ekblad
E
E
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D001284:Atrophy; D046508:Culture Techniques; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects* / Q000473:pathology*; D009479:Neuropeptides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide