Role of 5-hydroxytryptamine and mast cells in the tachykinin-induced contraction of rat trachea in vitro.
The in vivo bronchoconstrictor effect of tachykinins in Fisher 344 rats is accompanied by release into the airways of 5-hydroxytryptamine (5-HT). 5-HT is possibly derived from mast cells. In the present study the presumed mast cell-tachykinin interaction was studied in isolated trachea from Fisher 344 rats. Contractions induced by neurokinin A were largely reduced by the 5-HT antagonist methysergide, partially reduced by atropine, but not affected by hexamethonium or tetrodotoxin. Methysergide also inhibited the contractions induced by substance P, the tachykinin NK1 receptor agonist Ac[Arg6, Sar9, Met(O2)11]substance P-(6-11) and the mast cell depleting compound 48/80. Methysergide had no effect on contractions induced by carbachol or electrical field stimulation. Atropine significantly reduced contractions to 5-HT and completely inhibited contractions induced by electrical field stimulation. Histamine had no contractile effect. In vivo pretreatment with compound 48/80 significantly reduced the in vitro contractions to neurokinin A. Contractions to capsaicin were inhibited by methysergide and the tachykinin NK1 receptor antagonist (+/-)-RP67580 ((3alphaR,7alphaR)-(7,7-diphenyl-2-(1-imino-2-(2-methoxyp henylethyl)-perhydraisoinotol-4-one))). Substance P and neurokinin A caused 5-HT release in the organ bath, in a concentration- and time-dependent way. Atropine did not affect 5-HT release. Morphometric analysis showed that substance P and neurokinin A, but not carbachol, caused a significant increase in the number of degranulating mast cells in the muscular/submuscular region. In conclusion, tachykinins contract Fisher 344 rat trachea by releasing 5-HT from mast cells, an effect mediated by a tachykinin NK1 receptor.
Joos
G F
GF
Department of Respiratory Diseases, University Hospital, Ghent, Belgium. guy.joos@rug.ac.be
Lefebvre
R A
RA
Bullock
G R
GR
Pauwels
R A
RA
D000818:Animals; D016084:Bronchoconstriction / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D018040:Receptors, Neurokinin-1; D015320:Tachykinins; D012701:Serotonin; D013373:Substance P; D015288:Neurokinin A; D002211:Capsaicin