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. 1992 Aug;106(4):774–782. doi: 10.1111/j.1476-5381.1992.tb14412.x

Adenosine receptors on human airway epithelia and their relationship to chloride secretion.

E R Lazarowski 1, S J Mason 1, L Clarke 1, T K Harden 1, R C Boucher 1
PMCID: PMC1907665  PMID: 1327386

Abstract

1. We have characterized an adenosine receptor subtype present in human airway epithelial cells by measuring the changes in the intracellular levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and the rate of transepithelial Cl- secretion. 2. Primary cultures of human nasal epithelium obtained from excised surgical airway epithelial tissues and the cell lines BEAS39 and CF/T43 derived from human airway epithelium were grown on plastic dishes and labelled with [3H]-adenine for measurement of intracellular cyclic AMP accumulation. Primary cultures were loaded with the calcium indicator fura-2 to measure [Ca2+]i and studied as polarized, ion transporting epithelia on collagen matrix supports for measurement of Cl- secretion. 3. Adenosine analogues stimulated cyclic AMP accumulation with a rank order of potency characteristic of an A2-receptor: 5-N-ethyl-carboxamidoadenosine (NECA) greater than adenosine greater than R-phenylisopropyladenosine (R-PIA), 6-N-cyclopentyladenosine (CPA) greater than S-PIA. NECA increased cyclic AMP accumulation in normal and cystic fibrosis (CF) primary cells as well as in the CF/T43 and BEAS39 cell lines with K0.5 values ranging from 0.3 to 3 microM. Preincubation with NECA resulted in the homologous desensitization of airway epithelial cells. The effect of NECA was specifically inhibited by the adenosine receptor antagonist, aminophylline, in a competitive manner. 4. The A1-adenosine receptor agonists CPA and R-PIA did not inhibit isoprenaline-stimulated cyclic AMP accumulation in CF/T43 cells, and potentiating effects of the adenosine analogues were observed on forskolin-stimulated cyclic AMP accumulation. Adenosine analogues did not cause significant changes in intracellular Ca2+ ([Ca2+]i) in airway epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

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