Acute experimental esophagitis impairs signal transduction in cat lower esophageal sphincter circular muscle.
It has been previously shown that induction of experimental esophagitis in the cat by esophageal perfusion for 30 minutes with 0.1N HCl for 4 consecutive days results in a significant reduction of in vivo lower esophageal sphincter (LES) resting pressure and in vitro spontaneous tone without affecting esophageal response to KCl. It has also been shown that basal LES tone and LES contraction in response to acetylcholine depend on the release of calcium from intercellular stores, whereas esophageal contraction is mediated by extracellular calcium. The present report shows that esophageal acid perfusion impairs the transduction pathway mediating lower esophageal sphincter contraction in response to acetylcholine through release of intracellular calcium because LES strips and single cells no longer contract in response to acetylcholine if calcium is removed from the physiologic salt solution. This suggests that either the intracellular calcium stores or the release mechanisms that mediate maintenance of tone and contraction in response to acetylcholine may be damaged. However, the acid perfusion has no effect on the acetylcholine response in the esophagus, which is mediated by the influx of extracellular calcium. In the LES circular muscle, the injury results in reduced levels of inositol phosphates without affecting resting levels of 5'-cyclic adenosine monophosphate or 5'-cyclic guanosine monophosphate. The reduced levels of 1,4,5-inositol trisphosphate are consistent with impairment in the mechanisms responsible for release of intracellular calcium, although concurrent damage to calcium stores may also occur.
Biancani
P
P
Department of Medicine, Rhode Island Hospital, Providence.
Billett
G
G
Hillemeier
C
C
Nissensohn
M
M
Rhim
B Y
BY
Szewczak
S
S
Behar
J
J
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004533:Egtazic Acid / Q000494:pharmacology; D004941:Esophagitis / Q000378:metabolism*; D004943:Esophagogastric Junction / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D015398:Signal Transduction
D007295:Inositol Phosphates; D004533:Egtazic Acid; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium