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.
Matera
M G
MG
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, II University of Naples, Italy.
De Santis
D
D
D'Agostino
B
B
Pallotta
M
M
Vacca
C
C
Cazzola
M
M
Rossi
F
F
D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D014132:Trachea / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D014970:Xanthines; D010660:Phenylisopropyladenosine; D012701:Serotonin; D001285:Atropine; D004155:Diphenhydramine; D007650:Ketanserin; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D007213:Indomethacin