Effects of phosphodiesterase inhibitors on oesophageal neuromuscular functions

HyoJin Park, E. Clark, J. L. Conklin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The cyclic nucleotides adenosine 3′,5′-cyclic monophosphate (cAMP) and guanosine 3′,5′-cyclic monophosphate (cGMP) mediate the inhibitory effects of vasoactive intestinal polypeptide and nitric oxide on oesophageal smooth muscle. Phosphodiesterases (PDE) terminate their actions. We hypothesized that PDE inhibitors alter nerve-induced responses of oesophageal and lower oesophageal sphincter (LES) smooth muscle. An electrical field known to activate intrinsic oesophageal nerves was used to stimulate transverse muscle strips from the opossum oesophagus. This produced a contractile off-response from circular oesophageal muscle and a biphasic relaxation of the LES - an initial rapid relaxation (R1) and a slower sustained relaxation (R2). The effects on LES and oesophageal muscle of zaprinast (type V), zardaverine (type III/IV) and theophylline (non-specific) PDE inhibitors were explored. All three PDE inhibitors decreased LES tone and attenuated the off-response. Zaprinast and theophylline increased the latency of the off-response. Zaprinast prolonged R1, and slowed its recovery. It also increased the percentage relaxation of the second R2. Zardaverine increased the percentage relaxation of R2. Theophylline slowed the recovery of R2. PDEs play a role in maintaining LES tone and its recovery after LES relaxation. They may also modulate oesophageal motor activity.

Original languageEnglish
Pages (from-to)625-633
Number of pages9
JournalNeurogastroenterology and Motility
Volume15
Issue number6
DOIs
Publication statusPublished - 2003 Dec 1

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Lower Esophageal Sphincter
Phosphodiesterase Inhibitors
Theophylline
Muscles
Smooth Muscle
Opossums
Cyclic Nucleotides
Vasoactive Intestinal Peptide
Cyclic GMP
Phosphoric Diester Hydrolases
Adenosine
Esophagus
Reaction Time
Nitric Oxide
Motor Activity
zaprinast

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

Cite this

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Effects of phosphodiesterase inhibitors on oesophageal neuromuscular functions. / Park, HyoJin; Clark, E.; Conklin, J. L.

In: Neurogastroenterology and Motility, Vol. 15, No. 6, 01.12.2003, p. 625-633.

Research output: Contribution to journalArticle

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