Am. J. Respir. Cell Mol. Biol., Vol 10, No. 2, 02 1994, 230-236.
Relaxation of rabbit tracheal smooth muscle by adenine nucleotides: mediation by P2-purinoceptors
MO Aksoy and SG Kelsen
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
The relaxant action of adenine nucleotides was studied in isolated rabbit
trachealis to assess the presence of P2-purinoceptors in the airways, their
cellular location, and pharmacologic properties. Strips of tracheal smooth
muscle with intact epithelium were incubated in tissue baths and contracted
with 1 microM acetylcholine. Over a dose range of 0.1 microM to 1 mM, ATP
and ADP were significantly more potent than adenosine in relaxing tracheal
smooth muscle. Significant relaxations were also elicited by AMP-PCP,
AMP-CPP, and AMP-PNP, three ATP analogs stable to enzymatic hydrolysis to
adenosine. In the absence of acetylcholine, neither ATP nor AMP-CPP exerted
any contractile effect on the tracheal strips. In tissues selectively
denuded of epithelium, ATP-, ADP-, and AMP-PCP-induced relaxations were
markedly reduced. ATP-induced relaxation was also inhibited by the P2y-
purinoceptor antagonist Reactive Blue 2 (RB2) (50 to 300 microM) and
partially reduced by the cyclooxygenase inhibitor indomethacin (10 microM),
whereas adenosine-induced relaxation was not significantly affected by
these agents. These results suggest that ATP can induce smooth muscle
relaxation in acetylcholine-contracted tracheal strips through a distinct
P2-purinoceptor. This receptor appears to be located on the epithelium
where its relaxant effect is mediated in part by release of one or more
cyclooxygenase products. Additional relaxation at high ATP concentrations
may occur through enzymatic hydrolysis of ATP to adenosine and interaction
at P1-purinoceptors.
