The mechanism of tachykinin-induced bronchoconstriction in the rat.
The mammalian tachykinins substance P (SP) and neurokinin A (NKA) are known to be present in sensory airway nerves of animals and humans. We studied the effect of mammalian and nonmammalian tachykinins on the conducting airways of anesthetized, mechanically ventilated Fisher 344 rats. Dose-dependent increases in lung resistance and decreases in dynamic compliance occurred after the intravenous administration of eledoisin (E), kassinin (K), NKA, and SP. E, K, and NKA were more potent bronchoconstrictors than was SP. Neurokinin B (NKB) caused a similar decrease in dynamic compliance, but had no effect on lung resistance. This order of potency suggests a predominance of NK-2 receptors in the rat airways. Both atropine and the 5-hydroxytryptamine antagonist methysergide largely reduced the bronchoconstriction induced by E and SP. Vagotomy did not change this reaction, whereas pretreatment with the ganglion blocker hexamethonium slightly enhanced the bronchoconstrictor action of E and SP. Sodium cromoglycate and nedocromil sodium, 2 drugs that can inhibit mediator release from inflammatory cells, significantly reduced the bronchoconstrictor action of NKA. Ketotifen, an antihistamine with mast-cell-stabilizing properties, significantly reduced the bronchoconstriction induced by E, whereas the H1-receptor antagonist clemastine had no effect. We conclude that tachykinins cause bronchoconstriction in rats largely by an indirect mechanism, involving both acetylcholine and 5-hydroxytryptamine. We suggest that tachykinins cause bronchoconstriction by stimulation of postganglionic vagal nerve endings and mast cells.
Joos
G F
GF
Department of Respiratory Diseases, University Hospital, State University of Ghent, Belgium.
Pauwels
R A
RA
van der Straeten
M E
ME
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001980:Bronchi / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004600:Eledoisin / Q000494:pharmacology; D015286:Kassinin / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000502:physiology; D018039:Receptors, Tachykinin; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology / Q000502:physiology*; D014628:Vagotomy
D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D015286:Kassinin; D004600:Eledoisin; D015288:Neurokinin A; D015287:Neurokinin B