The role of central 5-HT receptors in the bronchoconstriction evoked by inhaled capsaicin in anaesthetised guinea-pigs.
The effects of intracisternal (i.c) injections of the 5-HT1A receptor agonists, buspirone and 8-OH-DPAT, and the antagonists WAY-100635; and (-)-pindolol, the 5-HT1B/1D receptor agonist sumatriptan and antagonist GR127935, the 5-HT2 receptor agonist DOI and the antagonist cinanserin, the 5-HT3 receptor antagonist granisetron, the alpha-adrenoceptor agonist clonidine and the antagonist idazoxan, the D2 receptor antagonists (-)-sulpiride and the 5-HT uptake inhibitor fluoxetine on capsaicin-evoked increase in tracheal inflation pressure (bronchoconstriction) were investigated in alpha-chloralose anaesthetised, neuromuscularly blocked, artificially ventilated guinea-pigs. Buspirone, 8-OH-DPAT and fluoxetine significantly potentiated while WAY-100635 (-)-pindolol and sumatriptan attenuated the evoked bronchoconstriction when applied i.c. Granisetron attenuated the response when applied i.v. but not when given i.c. The 5-HT2, alpha2-adrenoceptor and D2 dopamine receptor ligands did not have any significant effect on the evoked bronchoconstriction. Pretreatment i.v. with WAY-100635 alone had no effect on the capsaicin-evoked bronchoconstriction but blocked the potentiating action of i.c. buspirone. The effects of sumatriptan could be completely blocked by pretreatment i.v. with GR127935. Only DOI, in the presence (i.v.) of the peripheral acting 5-HT2 receptor antagonist BW501C67, caused a significant increase in baseline tracheal inflation pressure. It is concluded that activation of central 5-HT1A and 5-HT1B/1D receptors have opposing roles, facilitation and inhibition respectively, on the reflex activation of bronchoconstrictor vagal preganglionic neurones.
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, UK.
D J
DJ
Bootle
J J
JJ
Adcock
A G
AG
Ramage
D000280:Administration, Inhalation; D000818:Animals; D016084:Bronchoconstriction / Q000502:physiology*; D002211:Capsaicin; D005473:Fluoxetine / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents / Q000494:pharmacology*
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D005473:Fluoxetine; D002211:Capsaicin