Adenosine-mediated Cyclic AMP-dependent Inhibition of Ciliary Activity in Rabbit Tracheal Epithelium

Abstract

We wished to determine whether adenosine, a purine nucleotide, modulates activity of respiratory cilia and, to this end, we studied cultured rabbit tracheal epithelium in response to adenosine and related substances in vitro. Ciliary beat frequency (CBF) as determined by a photoelectric method was depressed by adenosine (10(-3) M), the maximal decrease from the baseline value (965 +/- 29 beats/min, mean +/- SE) being 31.6 +/- 5.0% (p less than 0.001). The adenosine A2-receptor agonist N-ethylcarboxamide adenosine had only a small effect on ciliary activity, whereas other adenosine analogs elicited decreases in CBF in a dose-dependent fashion. The order of potency of cilia-inhibitory action was N-cyclohexyladenosine (an agonist for adenosine A1-receptor) greater than phenylisopropyladenosine greater than adenosine greater than N-ethylcarboxamide adenosine. Intracellular cyclic AMP (cAMP) levels were decreased by 10(-3) M adenosine from 39.2 +/- 6.5 to 25.3 +/- 4.8 pM/mg protein (p less than 0.05). The effect of adenosine on CBF was enhanced by dipyridamole, an adenosine uptake inhibitor, and by deoxycoformycin, an adenosine deaminase inhibitor. The adenosine-induced decreases in CBF and cAMP content were reversed by 8-phenyltheophylline, an adenosine receptor antagonist. These results suggest that there is an adenosine A1-receptor on rabbit tracheal epithelium that inhibits adenylate cyclase, which may result in the impairment of respiratory ciliary activity, and that adenosine-induced ciliary inhibition may be modulated by adenosine uptake and its catabolism by airway epithelial cells.