Mechanisms involved in neurokinin-induced bronchoconstriction.
Substance P and neurokinin A have been shown to be present in the sensory airway innervation. In animals and in humans, both in vitro and in vivo, neurokinin A is a more potent bronchoconstrictor than substance P, suggesting that NK-2 receptors mediate their bronchoconstrictor action. Pharmacological studies on rat airways and in asthmatic patients have shown that a large part of the bronchoconstrictor effect of neurokinins is indirect. In animals (rabbit, rat and guinea-pig) neurokinins stimulate the release of acetylcholine from postganglionic cholinergic nerve fibres. Pharmacological studies performed on rat airways suggest that mast cells are also involved. In bronchoalveolar lavage studies in rats, performed immediately following the peak bronchoconstriction caused by the neurokinins, we were able to show that both substance P and neurokinin A cause histamine release into the airways. The physiological actions of neuropeptides are normally terminated by extracellular metabolism. Inhibitors of neutral metalloendopeptidase enhance the in vitro and in vivo bronchoconstrictor effect of the neurokinins. In our rat model, thiorphan not only enhanced the bronchoconstrictor effect of i.v. administered neurokinins, but also enhanced the airway histamine release caused by these sensory neuropeptides.
Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
G F
GF
Joos
R A
RA
Pauwels
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects*; D015288:Neurokinin A / Q000378:metabolism / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*
D013373:Substance P; D015288:Neurokinin A