Am. J. Respir. Crit. Care Med.,
Volume 158, Number 5, November 1998, 1479-1486
The Effects of 8-Hydroxy-2-(di-n-propylamino)tetralin
on the Cholinergic Contraction in Guinea Pig and
Human Airways In Vitro
LIEVEN J.
DUPONT,
JAN L.
PYPE,
MAURITS G.
DEMEDTS,
PAUL
DE LEYN,
GEORGES
DENEFFE,
and
GEERT M.
VERLEDEN
Pulmonary Pharmacology Unit, Laboratory of Pneumology and Department of Thoracic Surgery, University Hospital Gasthuisberg,
Katholieke Universiteit Leuven, Belgium
Electrical field stimulation of guinea pig tracheal strips and human bronchial rings, in vitro, evokes a
cholinergic contraction mediated by the release of acetylcholine. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a 5-HT1A and 5-HT7 agonist. In this study, we have investigated whether 8-OH-DPAT could modulate the cholinergic contraction in guinea pig and human airways in vitro. 8-OH-DPAT (1 to 30 µM) produced a concentration-dependent inhibition of the cholinergic contraction in
guinea pig tracheal strips with a maximal inhibition of 75.8% ± 4.7% (30 µM, 0.5 Hz). Pretreatment of the tissues with the 5- HT1/2/7 antagonist methysergide (10 to 30 µM) significantly attenuated the
inhibitory effects of 8-OH-DPAT (10 to 30 µM) on the cholinergic contraction. Pretreatment with ketanserin (10 µM), a 5-HT2 antagonist, tropisetron (1 µM), a 5-HT3/4 antagonist, SDZ 216-525 (1 to
10 µM) and pindobind (10 µM), both selective 5-HT1A antagonists, or capsaicin (10 µM), which depletes sensory nerves from neuropeptides, had no effect on the inhibition of the cholinergic contraction by 8-OH-DPAT (10 to 30 µM). 5-carboxamidotryptamine (5-CT) (10 to 100 µM), a 5-HT1/2/7 agonist,
partially mimicked the inhibitory effects of 8-OH-DPAT on the cholinergic contraction. 8-OH-DPAT
(10 to 30 µM) also inhibited the cholinergic contraction in human bronchial rings in vitro with a maximal inhibition of 46.2% ± 7.2% (30 µM, 1 Hz). SDZ 216-525 (10 µM) had no effect, whereas methysergide (30 µM) partially prevented the effect of 8-OH-DPAT in human airways. 8-OH-DPAT (30 µM)
did not displace the concentration-response curve to acetylcholine (10 nM-30 mM) in guinea pig and
human airways in vitro. These results suggest that 8-OH-DPAT inhibits the cholinergic contraction in
guinea pig and human airways in vitro through stimulation of prejunctional atypical 5-HT receptors,
possibly of the 5-HT7 subtype, located on postganglionic cholinergic nerves.
