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Modulation of ciliary beat frequency, not bend angle, by phosphodiesterase 1 during β2‐agonist stimulation in mouse bronchiolar ciliary cells
Author(s) -
Nakahari Takashi
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.697.1
Subject(s) - cilium , ibmx , chemistry , medicine , endocrinology , stimulation , biophysics , microbiology and biotechnology , biology , forskolin
The ciliary beating of the bronchiole plays a key role in the mucociliary transport. Bronchiolar ciliary cells were isolated from lungs of mice (C57Bl/6J) by an elastase treatment and their beating cilia were observed by a high‐speed camera (500Hz). A β2‐agonist, procaterol, increases ciliary beat frequency (CBF) and ciliary bend angle (CBA) mediated via cAMP. Procaterol consentration‐response studies demonstrated that the CBA curve shifts to a low concentration from the CBF curve; 10 pM procaterol increases CBA, but 10 nM procaterol increases CBA and CBF. However, isobutylmethylxanthine (IBMX) induced no shift of the CBA curve, suggesting that different phosphaodiesterase (PDE) subtypes regulate cAMP concentration in microdomains regulating CBA and CBF. A PDE1 inhibitor (8‐methoxymethyl IBMX) increased CBF, but not CBA. The procaterol actions were examined in ionomycin (IM)‐stimulated cells, because PDE1 is Ca 2+ ‐dependent. Procaterol (10 nM) increased CBA, but not CBF during IM stimulation. Previous studies revealed that the outer dyneins control CBF and the inner dyneins control CBA. Immunoelectronmicroscopy demonstrated that PDE1 is detected around nine doublet tubles in the bronchiolar cilia. In conclusion, in bronchiolar cilia, PDE1 is suggested to control cAMP accumulation in the microdomain regulating outer dyneins in the axoneme.