Regulation of pacemaker frequency in the murine gastric antrum

Tae Wan Kim, Elizabeth A.H. Beckett, Rhonda Hanna, Sang Don Koh, Tamás Ördög, Sean M. Ward, Kenton M. Sanders

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

PGE2 has been linked to the production of gastric arrhythmias such as tachygastria. The interstitial cells of Cajal (ICC) generate electrical rhythmicity in gastrointestinal muscles, and may therefore be a target for PGE2, in gastric muscles. We cultured ICC from the murine gastric antrum, verified that cells were Kit immunoreactive, and measured spontaneous slow waves. These events were caused by spontaneous inward (pacemaker) currents that were not blocked by nifedipine. Forskolin and 8-bromoadenosine 3′:5′-cyclic monophosphate (8-Br-cAMP) reduced the frequency of pacemaker currents in ICC and of slow waves in intact antral muscles. The effects of forskolin and 8-Br-cAMP were not blocked by inhibitors of protein kinase A, suggesting that cAMP has direct effects on pacemaker activity. PGE2, mimicked the effects of forskolin and 8-Br-cAMP on ICC, but increased slow-wave frequency in intact muscles. Therefore, the chronotropic effects of specific prostaglandin EP receptor agonists were examined. Butaprost and ONO-AE1-329, EP2 and EP4 receptor agonists, mimicked the effects of forskolin and 8-Br-cAMP on ICC and intact muscles. Sulprostone (EP3 > EP1 agonist), GR63799, and ONO-AE-248 (EP3 agonists) enhanced the frequencies of pacemaker currents in ICC and slow waves in intact muscles. The effects of sulprostone were not blocked by SC-19220, an EP1 receptor antagonist. These observations suggest that the positive chronotropic effects of PGE2 in intact muscles are mediated by EP3 receptor stimulation. The effects of PGE2 in intact muscles may be dependent upon the relative expression of EP receptors and/or proximity of receptors to sources of PGE2.

Original languageEnglish (US)
Pages (from-to)145-157
Number of pages13
JournalJournal of Physiology
Volume538
Issue number1
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Regulation of pacemaker frequency in the murine gastric antrum'. Together they form a unique fingerprint.

  • Cite this

    Kim, T. W., Beckett, E. A. H., Hanna, R., Koh, S. D., Ördög, T., Ward, S. M., & Sanders, K. M. (2002). Regulation of pacemaker frequency in the murine gastric antrum. Journal of Physiology, 538(1), 145-157. https://doi.org/10.1113/jphysiol.2001.012765