Defective modulation of colonic secretomotor neurons in a rabbit model of colitis.
The present in vitro study was conducted to investigate possible alterations in the control of colonic electrolyte transport in an experimental model of colitis. Intrarectal administration of trinitrobenzenesulfonic acid induced a colitis-like inflammation in the rabbit distal colon. Responses to amiloride and residual short-circuit current after this treatment were unchanged, suggesting that the absorptive and secretory mechanisms remained intact. Electrical field stimulation and vasoactive intestinal polypeptide, a candidate secretomotor neurotransmitter, both elicited similar responses in control and colitic tissue. This suggests that communication at the neuroepithelial junction was unimpaired. In untreated tissue, the effects of prostaglandin E2 (PGE2) and of acetylcholine were attenuated by tetrodotoxin, suggesting, therefore, that both play a role in the modulation of secretomotor neurons. In addition, PGE2 had an appreciable direct epithelial effect. Responses to both of these agonists were absent in colitis. The effects of N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate were unchanged in colitis, suggesting that altered PGE2 responsiveness may involve changes in epithelial receptor number, affinity, or in their ability to mediate an increase in adenosine 3',5'-cyclic monophosphate levels. It is concluded that this rabbit model of colitis exhibits 1) defects in the modulation of secretomotor neurons by acetylcholine and PGE2 and 2) an attenuated epithelial response to PGE2.
Division of Gastroenterology, Winthrop-University Hospital, Mineola, New York 11501.
J M
JM
Goldhill
R
R
Burakoff
V
V
Donovan
K
K
Rose
W H
WH
Percy
D000109:Acetylcholine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000294:innervation / Q000473:pathology / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007249:Inflammation; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D003994:Bucladesine; D000584:Amiloride; D014302:Trinitrobenzenesulfonic Acid; D015232:Dinoprostone; D000109:Acetylcholine