Premium
Effects of phosphodiesterase inhibitors on oesophageal neuromuscular functions
Author(s) -
Park H.,
Clark E.,
Conklin J. L.
Publication year - 2003
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1046/j.1350-1925.2003.00444.x
Subject(s) - zaprinast , theophylline , phosphodiesterase , medicine , endocrinology , cyclic guanosine monophosphate , muscle relaxation , adenosine , chemistry , cyclic adenosine monophosphate , aminophylline , rolipram , nitric oxide , biology , biochemistry , enzyme , cyclic gmp , receptor
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 (R 1 ) and a slower sustained relaxation (R 2 ). 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 R 1 , and slowed its recovery. It also increased the percentage relaxation of the second R 2 . Zardaverine increased the percentage relaxation of R 2 . Theophylline slowed the recovery of R 2 . PDEs play a role in maintaining LES tone and its recovery after LES relaxation. They may also modulate oesophageal motor activity.