The role of central 5-HT receptors in the bronchoconstriction evoked by inhaled capsaicin in anaesthetised guinea-pigs

Abstract

The effects of intracisternal (i.c) injections of the 5-HT 1A receptor agonists, buspirone and 8-OH-DPAT, and the antagonists WAY-100635; and (-)-pindolol, the 5-HT 1B/1D receptor agonist sumatriptan and antagonist GR127935, the 5-HT 2 receptor agonist DOI and the antagonist cinanserin, the 5-HT 3 receptor antagonist granisetron, the α 2-adrenoceptor agonist clonidine and the antagonist idazoxan, the D 2 receptor antagonists (-)-sulpiride and the 5-HT uptake inhibitor fluoxetine on capsaicin-evoked increase in tracheal inflation pressure (bronchoconstriction) were investigated in α-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-HT 2, α 2-adrenoceptor and D 2 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-HT 2 receptor antagonist BW501C67, caused a significant increase in baseline tracheal inflation pressure. It is concluded that activation of central 5-HT 1A and 5-HT 1B/1D receptors have opposing roles, facilitation and inhibition respectively, on the reflex activation of bronchoconstrictor vagal preganglionic neurones.