The effect of tegaserod on esophageal submucosal glands bicarbonate and mucin secretion.
Tegaserod, a 5-HT4 partial agonist, was shown to reduce esophageal acid exposure in patients with gastroesophageal reflux disease; however, its mechanism of action is poorly understood. Therefore, we have examined the effect of tegaserod on luminal bicarbonate and mucin secretion in the isolated perfused pig esophagus. We also studied its role in esophageal protection using SMG-bearing pig esophagus in comparison to the rabbit esophagus, which is devoid of them. The tissues were mounted in Ussing chambers, and acid injury was replicated by exposing the lumen to acid (pH 1.6) or acid/pepsin (pH 2.5). In pig esophagus, tegaserod increased bicarbonate secretion, but had no effect on basal mucin secretion. In Ussing chambers, tegaserod reduced injury to pig, but not rabbit esophagus exposed to acid (pH 2.5) plus pepsin. These results indicate that tegaserod stimulates SMG bicarbonate secretion, an effect that likely accounts for the observed protection against acid-pepsin injury to pig, but not rabbit, esophagus.
Abdulnour-Nakhoul
Solange
S
Southeast Louisiana Veterans Health Care Network, and Departments of Medicine and Physiology, Tulane University School of Medicine, c/o Tulane Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA. solange@tulane.edu
Tobey
Nelia A
NA
Nakhoul
Nazih L
NL
Wheeler
Scott A
SA
Vanegas
Ximena
X
Orlando
Roy C
RC
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D006851:Hydrochloric Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009077:Mucins / Q000378:metabolism*; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D010434:Pepsin A / Q000494:pharmacology; D011817:Rabbits; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013552:Swine
D001639:Bicarbonates; D007211:Indoles; D009077:Mucins; D017366:Serotonin Receptor Agonists; C105050:tegaserod; D010434:Pepsin A; D006851:Hydrochloric Acid