Effect of 5-HT1A receptor agonist, 8-OH-DPAT, on cough responses in the conscious guinea pig.
We have studied the role for 5-hydroxytryptamine (5-HT) in the modulation of the cough reflex by examining the effect of a selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on cough and respiratory rate in conscious guinea pigs. Animals were placed in a box and exposed to the tussive agent citric acid (0.5 M) for 10 min, 3 min after terbutaline (0.05 mg/kg i.p.) was administered to prevent bronchoconstriction. 8-OH-DPAT inhibited at low doses (0.008 and 0.016 mg/kg) but potentiated at high doses (0.25 and 0.5 mg/kg) the citric acid-induced number of coughs, but dose-dependently increased respiratory rate. Methysergide (0.05-5 mg/kg), a 5HT1 and 5HT2 receptor antagonist, and ketanserin (0.005 mg/kg), a 5HT2 receptor antagonist, had no effects on cough or respiratory rate. Methysergide inhibited the increased cough responses and respiratory rate induced by 8-OH-DPAT at high doses, while ketanserin was without effect. These results suggest that 8-OH-DPAT may induce both in inhibition and activation of the cough reflex, the latter involving central 5HT1-receptor activation.
Stone
R A
RA
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Barnes
P J
PJ
Chung
K F
KF
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003371:Cough; D006168:Guinea Pigs; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin