Mechanism of Rho-kinase-mediated Ca2+-independent contraction in aganglionic smooth muscle in a rat model of Hirschsprung's disease

Junko Akiyoshi, Satoshi Ieiri, Takanori Nakatsuji, Tomoaki Taguchi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: Lack of ganglion cells is the main cause of bowel movement disorder in Hirschsprung's disease. Because smooth muscle is the primary organ, the properties of intestinal smooth muscle need to be investigated. We therefore investigated the reactivity of the contractile system and the mechanism of contraction in aganglionic intestinal smooth muscle. Methods: Colonic smooth muscle strips from endothelin-B receptor gene-deficient [EDNRB(-/-)] rats were loaded with the Ca2+ indicator dye fura-PE3/AM and changes in fluorescence intensity were monitored. The intracellular calcium concentration ([Ca2+]i) and force development in the strips were measured simultaneously. Results: The force induced by 10 μM substance P (SP) was higher than that induced by 60 mM K+ depolarization (control), whereas [Ca2+]i elevation induced by 10 μM SP was less than that induced by 60 mM K+ in all segments. Pretreatment with the Rho-kinase inhibitor Y-27632 inhibited force development more strongly in EDNRB(-/-) aganglionic segments than in EDNRB(+/+) ganglionic segments. However, [Ca 2+]i was higher in EDNRB(-/-) aganglionic segments than in EDNRB(+/+) ganglionic segments. Conclusions: The Ca2+-independent pathway involving Rho-kinase was hyperactivated in EDNRB(-/-) aganglionic segments. This phenomenon is assumed to compensate for Ca2+ channel downregulation and Ca2+-dependent contraction. From a clinical point of view, the motility of aganglionic intestine would be controllable with the control of Ca2+-independent contraction before definitive operations in Hirschsprung's disease.

Original languageEnglish
Pages (from-to)955-960
Number of pages6
JournalPediatric surgery international
Volume25
Issue number11
DOIs
Publication statusPublished - Nov 1 2009

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Surgery

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