Effects of adenosine and theophylline on canine tracheal smooth muscle tone

The postulated mechanisms by which theophylline induces relaxation of airway smooth muscle include, among others, inhibition of cyclic nucleotide phosphodiesterase(s) and antagonism of adenosine-induced contraction. This latter possibility was examined by investigation of the interaction of theophylline and adenosine in canine tracheal smooth muscle preparations. Adenosine did not alter basal tone i.e. there is no evidence of a contractile response. However, when contraction was induced with methacholine, adenosine caused relaxation. It appears that this relaxation occurred as a consequence of the combination of adenosine with a site within the smooth muscle cell. The prior addition of theophylline (10(-6)-10(-3) M) did not alter adenosine-induced relaxation and in the reverse experiment, the prior addition of adenosine (10(-6)-10(-3) M) did not alter the relaxation produced by theophylline. It is concluded that adenosine relaxes canine tracheal smooth muscle by combination with an intracellular site, rather than a receptor on the cell surface. The hypothesis that theophylline relaxes airways smooth muscle by antagonism of adenosine or that adenosine antagonizes theophylline was not supported by our data.