Adenosine activation of A2B receptor(s) is essential for stimulated epithelial ciliary motility and clearance

Diane S. Allen-Gipson, Michael R. Blackburn, Daniel J. Schneider, Hui Zhang, DeAndre L. Bluitt, Justin C. Jarrell, Daniel Yanov, Joseph Harold Sisson, Todd A Wyatt

Research output: Contribution to journalArticle

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Abstract

Mucociliary clearance, vital to lung clearance, is dependent on cilia beat frequency (CBF), coordination of cilia, and the maintenance of periciliary fluid. Adenosine, the metabolic breakdown product of ATP, is an important modulator of ciliary motility. However, the contributions of specific adenosine receptors to key airway ciliary motility processes are unclear. We hypothesized that adenosine modulates ciliary motility via activation of its cell surface receptors (A1, A2A, A2B, or A3). To test this hypothesis, mouse tracheal rings (MTRs) excised from wild-type and adenosine receptor knockout mice (A1, A2A, A2B, or A3, respectively), and bovine ciliated bronchial epithelial cells (BBECs) were stimulated with known cilia activators, isoproterenol (ISO; 10 μM) and/or procaterol (10 μM), in the presence or absence of 5=-(Nethylcarboxamido) adenosine (NECA), a nonselective adenosine receptor agonist [100 nM (A1, A2A, A3); 10 μM (A2B)], and CBF was measured. Cells and MTRs were also stimulated with NECA (100 nM or 10 μM) in the presence and absence of adenosine deaminase inhibitor, erythro-9- (2-hydroxy-3-nonyl) adenine hydrochloride (10 μM). Both ISO and procaterol stimulated CBF in untreated cells and/or MTRs from both wild-type and adenosine knockout mice by ∼3 Hz. Likewise, CBF significantly increased ∼2-3 Hz in BBECs and wild-type MTRs stimulated with NECA. MTRs from A1, A2A, and A3 knockout mice stimulated with NECA also demonstrated an increase in CBF. However, NECA failed to stimulate CBF in MTRs from A2B knockout mice. To confirm the mechanism by which adenosine modulates CBF, protein kinase activity assays were conducted. The data revealed that NECA-stimulated CBF is mediated by the activation of cAMP-dependent PKA. Collectively, these data indicate that purinergic stimulation of CBF requires A2B adenosine receptor activation, likely via a PKA-dependent pathway.

Original languageEnglish (US)
Pages (from-to)L171-L180
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number2
DOIs
StatePublished - Aug 1 2011

Fingerprint

Adenosine A2B Receptors
Cilia
Adenosine
Knockout Mice
Procaterol
Purinergic P1 Receptors
Epithelial Cells
Adenosine Deaminase Inhibitors
Purinergic P1 Receptor Agonists
Mucociliary Clearance
Cell Surface Receptors
Isoproterenol
Protein Kinases

Keywords

  • Bovine bronchial epithelial cells
  • Knockout mouse model
  • Mucociliary clearance

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Adenosine activation of A2B receptor(s) is essential for stimulated epithelial ciliary motility and clearance. / Allen-Gipson, Diane S.; Blackburn, Michael R.; Schneider, Daniel J.; Zhang, Hui; Bluitt, DeAndre L.; Jarrell, Justin C.; Yanov, Daniel; Sisson, Joseph Harold; Wyatt, Todd A.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 301, No. 2, 01.08.2011, p. L171-L180.

Research output: Contribution to journalArticle

Allen-Gipson, Diane S. ; Blackburn, Michael R. ; Schneider, Daniel J. ; Zhang, Hui ; Bluitt, DeAndre L. ; Jarrell, Justin C. ; Yanov, Daniel ; Sisson, Joseph Harold ; Wyatt, Todd A. / Adenosine activation of A2B receptor(s) is essential for stimulated epithelial ciliary motility and clearance. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2011 ; Vol. 301, No. 2. pp. L171-L180.
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