Alimentary TractActivation of the GABAB receptor inhibits transient lower esophageal sphincter relaxations in dogs☆
Section snippets
General
Twelve adult Labrador retrievers (6 male) and 3 beagles (2 male) were trained to stand in a Pavlov sling. Mucosa-to-skin esophagostomies were formed, and the dogs were allowed to recover completely before any experiments were performed. The dogs were used in drug-screening experiments, but a washout of at least 2 days was allowed before further experimentation. All experiments were approved by the local ethics committee for animal experiments.
Motility measurement
The experiments have been described in detail
Results
The total number of TLESRs differed markedly between dogs but was fairly constant within each dog (n = 107 control experiments, all dogs included). No age-dependent changes in the frequency of TLESRs in control studies have been found over a period of >3 years. The control values for motility parameters are given in Table 1.
Discussion
The present study shows for the first time that the selective GABAB-receptor agonist baclofen dose-dependently inhibits TLESR. The effect of baclofen is not restricted to dogs, because an identical effect has been observed in ferrets.31 Baclofen reduced the frequency of TLESRs and prolonged the latency to the first TLESR. However, TLESRs recorded in the presence of baclofen were indistinguishable in their pressure profile from those observed in control experiments. TLESRs are believed to be
Acknowledgements
The authors thank L. A. Blackshaw, J. Dent, S. J. H. Brookes, and R. H. Holloway for helpful discussions; M. Wilsson and L. Björklund for performing the surgery; and C. Ekman for assistance with the statistical analyses.
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Address requests for reprints to: Anders Lehmann, Ph.D., Gastrointestinal Pharmacology, Astra Zeneca R & D Mölndal S-431 83 Mölndal, Sweden. e-mail: [email protected]; fax: (46) 31-776-3747.