Counterregulation of a prokinetic calcium-dependent mechanism by cAMP-dependent agents in isolated segments of terminal ileum.
The ill-understood complex of the irritable bowel syndrome comprises a group of intestinal motility disorders characterized by increased intraluminal pressures and decreased transit times. Elucidation of mechanisms which modulate gut motility may lead to the development of rational therapy for this prevalent problem. The purpose of this study was firstly to evaluate the interaction of cAMP-dependent agents (vasoactive intestinal polypeptide (VIP), norepinephrine (NE), and forskolin (FK)) on carbachol (Ca2+)-initiated motility and secondly to determine if a neural component of motility modulation existed by testing if the effect of cAMP-dependent agents was reversed by tetrodotoxin-induced neural blockade. Motility was measured in isolated segments of terminal ileum harvested from rabbits using perfusion manometry and quantitated by integration, expressed as mm Hg/min. Carbachol caused a concentration-dependent increase in measured motor activity (half-effective dose = 10(-7) M). VIP, NE, and FK each caused a concentration-dependent inhibition of carbachol-stimulated phasic contractions. TTX 10(-6) M failed to block the inhibitory actions of NE. In conclusion, these results suggest that cAMP-dependent mechanisms may inhibit gut motility induced by a cholinergic (Ca2+)-mediated agonist and that this process is mediated by a nonneural mechanism.
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510.
S J
SJ
Ferzoco
I M
IM
Modlin
G H
GH
Ballantyne
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine