Interplay between the NO pathway and elevated [Ca2+]i enhances ciliary activity in rabbit trachea
N Uzlaner, Z Priel - The Journal of Physiology, 1999 - Wiley Online Library
N Uzlaner, Z Priel
The Journal of Physiology, 1999•Wiley Online Library1 Average intracellular calcium concentration ([Ca2+] i) and ciliary beat frequency (CBF)
were simultaneously measured in rabbit airway ciliated cells in order to elucidate the
molecular events that lead to ciliary activation by purinergic stimulation. 2 Extracellular ATP
and extracellular UTP caused a rapid increase in both [Ca2+] i and CBF. These effects were
practically abolished by a phospholipase C inhibitor (U‐73122) or by suramin. 3 The effects
of extracellular ATP were not altered: when protein kinase C (PKC) was inhibited by either …
were simultaneously measured in rabbit airway ciliated cells in order to elucidate the
molecular events that lead to ciliary activation by purinergic stimulation. 2 Extracellular ATP
and extracellular UTP caused a rapid increase in both [Ca2+] i and CBF. These effects were
practically abolished by a phospholipase C inhibitor (U‐73122) or by suramin. 3 The effects
of extracellular ATP were not altered: when protein kinase C (PKC) was inhibited by either …
- 1Average intracellular calcium concentration ([Ca2+]i) and ciliary beat frequency (CBF) were simultaneously measured in rabbit airway ciliated cells in order to elucidate the molecular events that lead to ciliary activation by purinergic stimulation.
- 2Extracellular ATP and extracellular UTP caused a rapid increase in both [Ca2+]i and CBF. These effects were practically abolished by a phospholipase C inhibitor (U‐73122) or by suramin.
- 3The effects of extracellular ATP were not altered: when protein kinase C (PKC) was inhibited by either GF 109203X or chelerythrine chloride, or when protein kinase A (PKA) was inhibited by RP‐adenosine 3′, 5′‐cyclic monophosphothioate triethylamine (Rp‐cAMPS).
- 4Activation of PKC by phorbol 12‐myristate, 13‐acetate (TPA) had little effect on CBF or on [Ca2+]i, while activation of PKA by forskolin or by dibutyryl‐cAMP led to a small rise in CBF without affecting [Ca2+]i.
- 5Direct activation of protein kinase G (PKG) with dibutyryl‐cGMP had a negligible effect on CBF when [Ca2+]i was at basal level. However, dibutyryl‐cGMP strongly elevated CBF when [Ca2+]i was elevated either by extracellular ATP or by ionomycin.
- 6The findings suggest that the initial rise in [Ca2+]i induced by extracellular ATP activates the NO pathway, thus leading to PKG activation. In the continuous presence of elevated [Ca2+]i the stimulated PKG then induces a robust enhancement in CBF. In parallel, activated PKG plays a central role in Ca2+ influx via a still unidentified mechanism, and thus, through positive feedback, maintains CBF close to its maximal level in the continuous presence of ATP.
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