THE ROLE OF CENTRAL 5-HT RECEPTORS IN THE BRONCHOCONSTRICTION EVOKED BY INHALED CAPSAICIN IN ANESTHETIZED 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 antagoni st GR127935, the 5-HT2 receptor agonist DOI and the antagonist cinanse rin, the 5-HT3 receptor antagonist granisetron, the alpha(2)-adrenocep tor agonist clonidine and the antagonist idazoxan, the D-2 receptor an tagonists (-)-sulpiride and the 5-HT uptake inhibitor fluoxetine on ca psaicin-evoked increase in tracheal inflation pressure (bronchoconstri ction) were investigated in alpha-chloralose anaesthetised, neuromuscu larly blocked, artificially ventilated guinea-pigs. Buspirone, 8-OH-DP AT and fluoxetine significantly potentiated while WAY-100635 (-)-pindo lol and sumatriptan attenuated the evoked bronchoconstriction when app lied i.c. Granisetron attenuated the response when applied i.v. but no t when given i.c. The 5-HT2, alpha(2)-adrenoceptor and D-2 dopamine re ceptor ligands did not have any significant effect on the evoked bronc hoconstriction. Pretreatment i.v. with WAY-100635 alone had no effect on the capsaicin-evoked bronchoconstriction but blocked the potentiati ng action of i.c. buspirone. The effects of sumatriptan could be compl etely blocked by pretreatment i.v. with GR127935. Only DOI, in the pre sence (i.v.) of the peripheral acting 5-HT2 receptor antagonist BW501C 67, caused a significant increase in baseline tracheal inflation press ure. It is concluded that activation of central 5-HT1A and 5-HT1B/1D r eceptors have opposing roles, facilitation and inhibition respectively , on the reflex activation of bronchoconstrictor vagal preganglionic n eurones. (C) 1998 Elsevier Science Ltd. All rights reserved.