A potentiating effect of endogenous NO in the physiologic secretion from airway submucosal glands

Tsutomu Tamada, Masayuki Nara, Hiroshi Kanatsuka, Miyuki Nagaoka, Ryoji Koshida, Gen Tamura, Toshio Hattori

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

It is known that several second messengers, such as Ca2+ or cAMP, play important roles in the intracellular pathway of electrolyte secretion in tracheal submucosal gland. However, the participation of cGMP, and therefore nitric oxide (NO), is not well understood. To investigate the physiologic role of NO, we first examined whether tracheal glands can synthesize NO in response to acetylcholine (ACh), and then whether endogenous NO has some effects on the ACh-triggered ionic currents. From the experiments using the NO-specific fluorescent indicator 4,5-diaminofluorescein diacetate salt (DAF-2DA), we found that a physiologically relevant low dose of ACh (100 nM) stimulated the endogenous NO synthesis, and it was almost completely suppressed in the presence of the nonspecific NO synthase (NOS) inhibitor Nω-Nitro-L-arginine Methyl Ester Hydrochloride (L-NAME) or the neuronal NOS (nNOS)-specific inhibitor 7-Nitroindazole (7-NI). Patch-clamp experiments revealed that both the NOS inhibitors (L-NAME or 7-NI) and cGK inhibitors (KT-5823 or Rp-8-Br-cGMP) partially decreased ionic currents induced by 30 nM of ACh, but not in the case of 300 nM of ACh. Our results indicate that NO can be synthesized through the activation of nNOS endogenously and has potentiating effects on the gland secretion, under a physiologically relevant ACh stimulation. When cells were stimulated by an inadequately potent dose of ACh, which caused an excess elevation in [Ca2+]i, the cells were desensitized. Therefore, due to NO, gland cells become more sensitive to calcium signaling and are able to maintain electrolyte secretion without desensitization.

Original languageEnglish
Pages (from-to)357-365
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume37
Issue number3
DOIs
Publication statusPublished - 2007 Sep

Keywords

  • Calcium
  • Chloride secretion
  • Cholinergic receptor
  • Clca
  • Kca

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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