ROLE OF 5-HYDROXYTRYPTAMINE IN MEDIATING ADENOSINE-INDUCED AIRWAY CONTRACTION

We have investigated the role of 5-hydroxytryptamine (5-HT) on adenosi ne-induced guinea-pig trachea contraction. R-N-6-phenylisopropyladenos ine (R-PIA), an A(1) receptor subtype agonist, induced a concentration -dependent contraction of tracheal rings. The pD(2) values were 7.43 /- 0.26. A 30-min pretreatment with 1,3-dipropyl-8-amino-4-clorophenyl -xantine (PACPX), a selective A(1) receptor antagonist, shifted to the right the R-PIA concentration effect curves. Ketanserin (1 mu M), a 5 -HT2 receptor antagonist, also caused a rightward shift of the R-PIA c oncentration-effect curves. The changes for the pD(2) values comparing the controls and the tissues incubated with ketanserin were statistic ally significant (P<0.05). In the same experimental conditions, neithe r atropine (1 mu M), nor diphenydramine (1 mu M), nor indomethacin (5 mu M) showed any effects. The challenge of R-PIA (1 mu M) with said su bstances 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 exper imental conditions, this effect did not occur in the controls. Our dat a support the hypothesis that 5-HT plays a role in adenosine-induced a irway contraction.