The effect of tachykinins on sheep bronchomotor tone.
The mammalian tachykinin neuropeptides substance P (SP) and neurokinin A (NKA) are present in the airways of several species and are involved in control of bronchomotor tone. We investigated the effect of SP and NKA on various respiratory and cardiovascular parameters in anaesthetized sheep. Dose-dependent decrease in dynamic compliance (Cdyn) and increase in respiratory resistance (RL) occurred with intravenous administration of SP. The predominant effect of NKA was on Cdyn with little or no effect on RL. Consequently SP is a more potent bronchoconstrictor than NKA in the sheep and affects both central and peripheral airway tone. The sensitivity to SP and NKA and the order of potency found suggests the NK-1 receptor predominates in sheep airways. Atropine and the ganglion blocker hexamethonium markedly reduced the bronchoconstriction caused by SP. SP and NKA were equipotent in causing a significant reduction in respiratory rate. SP caused a fall in mean blood pressure while NKA caused mild vasoconstriction. Neither peptide affected heart rate. We concluded that SP is a more potent bronchoconstrictor than NKA in the sheep and that the mechanism of action is mainly indirect involving modulation of postganglionic cholinergic nerve endings.
Corcoran
B M
BM
Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall.
Haigh
A L
AL
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D016084:Bronchoconstriction / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007275:Injections, Intravenous; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D015288:Neurokinin A / Q000494:pharmacology; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000502:physiology; D012756:Sheep / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D006584:Hexamethonium Compounds; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D013373:Substance P; D001285:Atropine; D015288:Neurokinin A