ATP and A1 adenosine receptor agonists mobilize intracellular calcium and activate K+ and Cl- currents in normal and cystic fibrosis airway epithelial cells

Michela Rugolo, Teresa Mastrocola, Claudia Whörle, Andrea Rasola, Dieter C. Gruenert, Giovanni Romeo, Luis J V Galietta

Research output: Contribution to journalArticle

Abstract

The effect of purinergic compounds on [Ca2+]i and membrane currents of cell lines derived from the airway epithelium of normal and cystic fibrosis individuals has been investigated. 2-Chloroadenosine (2-CADO), as well as other agonists of the A1 adenosine receptors, causes a transient elevation of cytosolic [Ca2+] that is antagonized by the A1 adenosine receptor antagonist 8-cyclopentyl-1,3 dipropylxanthine (DPCPX). ATP is also effective, but at a lower extent. The [Ca2+]. increase induced by 2-CADO and ATP is abolished by preincubation with phorbol 12-myristate 13-acetate and the Ca2+-ATPase inhibitor thapsigargin. This latter result suggests that purinergic agonists mobilize Ca2+ from inositol 1,4,5-trisphosphate-sensitive stores. Pertussis toxin completely inhibits the effect of 2-CADO, whereas only it partially affects that of ATP, suggesting the involvement of different types of G proteins. Perforated patch clamp experiments carried out in both current clamp and voltage clamp modes show that 2-CADO and ATP activate K+- and Cl--selective membrane currents, with a mechanism inhibited by preincubation with DPCPX and thapsigargin. These data indicate that activation of adenosine A1 receptor, in a similar way to ATP receptor, causes [Ca2+],- increase and ion channels activation through a transduction mechanism that is not impaired in cystic fibrosis airway epithelial cells.

Original languageEnglish
Pages (from-to)24779-24784
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number33
Publication statusPublished - Nov 25 1993

ASJC Scopus subject areas

  • Biochemistry

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    Rugolo, M., Mastrocola, T., Whörle, C., Rasola, A., Gruenert, D. C., Romeo, G., & Galietta, L. J. V. (1993). ATP and A1 adenosine receptor agonists mobilize intracellular calcium and activate K+ and Cl- currents in normal and cystic fibrosis airway epithelial cells. Journal of Biological Chemistry, 268(33), 24779-24784.