Cyclic GMP-mediated activation of a glibenclamide-sensitive mechanism in the rabbit sphincter of Oddi

Reka Sari, Barna Peitl, Peter Kovacs, Janos Lonovics, Attila Palvolgyi, Peter Hegyi, Istvan Nagy, Jozsef Nemeth, Zoltan Szilvassy, Robert Porszasz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We investigated whether glibenclamide-sensitive potassium channels are involved in cyclic GMP (cGMP)-mediated relaxation of the rabbit Oddi's sphincter. Changes in isometric tension were measured in the presence of atropine (1 μM) and guanethidine (4 μM). Concentration-response curves for nitroglycerin, vasoactive intestinal polypeptide (VIP), and sodium nitroprusside (SNP) were shifted to the right in the presence of (p-chloro-D-Phe6, Leu17)-VIP (VIPa), a VIP receptor antagonist. Glibenclamide (1 μM) attenuated the relaxations to VIP, nitroglycerin, or 8-bromo cGMP. In the presence of tetrodotoxin (TTX), glibenclamide attenuated relaxations to VIP without effect on those to nitroglycerin. Furthermore, nitroglycerin increased both cAMP and cGMP concentrations, however, it failed to increase the tissue cAMP concentration in the presence of TTX. VIPa also blocked the increase in content of either cyclic nucleotide. VIP increased cAMP with a TTX-sensitive increase in cGMP content. 8-Bromo cGMP (1 μM) significantly increased the tissue cAMP content. This was blocked by either TTX or VIPa (both 1 μM). We conclude that ATP-sensitive potassium channel (KATP) activation contributes to cGMP-mediated relaxation of the Oddi's sphincter of the rabbit. Activation of KATP results from a cyclic AMP-mediated process due to cGMP-dependent VIP release from neurons.

Original languageEnglish
Pages (from-to)514-520
Number of pages7
JournalDigestive Diseases and Sciences
Volume49
Issue number3
DOIs
Publication statusPublished - Mar 1 2004

Keywords

  • Cyclic AMP
  • Cyclic GMP
  • Glibenclamide
  • Nitrates
  • Oddi's sphincter
  • Vasoactive intestinal polypeptide

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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