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

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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 < 0.001). The adenosine A2-receptor agonist N-ethylcarboxamideadenosine 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 cilioinhibitory action was N-cyclohexyladenosine (an agonist for adenosine A1-receptor) > phenylisopropyladenosine > adenosine > N-ethylcarboxamideadenosine. 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 < 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, and 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.