Role of 5-hydroxytryptamine in mediating adenosine-induced airway contraction

We have investigated the role of 5-hydroxytryptamine (5-HT) on adenosine-induced guinea-pig trachea contraction. R-N6-phenylisopropyladenosine (R-PIA), an A1 receptor subtype agonist, induced a concentration-dependent contraction of tracheal rings. The pD2 values were 7.43 +/- 0.26. A 30-min pretreatment with 1,3-dipropyl-8-amino-4-clorophenylxantine (PACPX), a selective A1 receptor antagonist, shifted to the right the R-PIA concentration effect curves. Ketanserin (1 microM), a 5-HT2 receptor antagonist, also caused a rightward shift of the R-PIA concentration-effect curves. The changes for the pD2 values comparing the controls and the tissues incubated with ketanserin were statistically significant (P < 0.05). In the same experimental conditions, neither atropine (1 microM), nor diphenydramine (1 microM), nor indomethacin (5 microM) showed any effects. The challenge of R-PIA (1 microM) with said substances induced a release of 5-HT (4.8 +/- 0.20 fmol/ml) from guinea-pig trachea in presence or in absence of epithelium; in the same experimental conditions, this effect did not occur in the controls. Our data support the hypothesis that 5-HT plays a role in adenosine-induced airway contraction.