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The Effect of Tegaserod on Esophageal Submucosal Glands Bicarbonate and Mucin Secretion

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Abstract

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.

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Notes

  1. On 30 March 2007 Novartis announced it was complying with a request from the Food and Drug Administration (FDA) to suspend US marketing and sales of tegaserod due to an updated analysis of clinical trial data identifying a small but statistically significant imbalance in the number of cardiovascular ischemic events in patients taking tegaserod. The data showed that events including heart attack, stroke, and unstable angina occurred in 13 out of 11,614 patients treated with tegaserod (0.11%), compared to 1 case in 7,031 placebo-treated patients (0.01%). These cardiovascular ischemic events occurred in patients who had pre-existing cardiovascular disease and/or cardiovascular risk factors. There is no demonstrated causal relationship between tegaserod and these events.

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Acknowledgments

This study was funded by a VA Merit grant to SAN, grants from Novartis and NIH DK 036013 to RCO, and a NIH grant DK-62295-01A1 to NLN. Dr. Roy C. Orlando has served as an ad-hoc consultant to Novartis, Astra Zeneca, Proctor and Gamble. The study design, collection, analysis, and interpretation of the data were totally independent of the funding sources. We thank Ms. Anita Verdun for generously donating the pig tissues.

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Authors and Affiliations

  1. Southeast Louisiana Veterans Health Care Network and The Departments of Medicine and Physiology, Tulane University School of Medicine, c/o Tulane Medical Center, SL 45, 1430 Tulane Avenue, New Orleans, LA, 70112-2699, USA

    Solange Abdulnour-Nakhoul, Nelia A. Tobey, Nazih L. Nakhoul, Scott A. Wheeler, Ximena Vanegas & Roy C. Orlando

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  1. Solange Abdulnour-Nakhoul
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  2. Nelia A. Tobey
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  3. Nazih L. Nakhoul
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  4. Scott A. Wheeler
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  5. Ximena Vanegas
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  6. Roy C. Orlando
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Correspondence to Solange Abdulnour-Nakhoul.

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Abdulnour-Nakhoul, S., Tobey, N.A., Nakhoul, N.L. et al. The Effect of Tegaserod on Esophageal Submucosal Glands Bicarbonate and Mucin Secretion. Dig Dis Sci 53, 2366–2372 (2008). https://doi.org/10.1007/s10620-007-0170-1

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  • DOI: https://doi.org/10.1007/s10620-007-0170-1

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