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SENSORY NERVES IN THE AIRWAYS AS A TARGET FOR DRUG DEVELOPMENT
Author(s) -
Rechtman M. P.
Publication year - 1992
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1992.tb00394.x
Subject(s) - substance p , chemistry , bronchoconstriction , agonist , stimulation , eledoisin , (+) naloxone , pharmacology , endocrinology , medicine , atropine , tachykinin receptor , capsaicin , phenoxybenzamine , neurokinin a , receptor , opioid , neuropeptide , biochemistry , asthma
SUMMARY 1. Electrical stimulation (2.5–10 Hz, 80 V, 1 ms for 15 s) within the spinal canal of the pithed guinea‐pig pretreated with atropine, D‐tubocurarine and pentolinium caused a bronchoconstrictor response, indicated by a rise of insufflation pressure. 2. The magnitude of these non‐cholinergic neuronal bronchoconstrictor responses were frequency‐dependent, capsaicin‐sensitive and temperature‐dependent. 3. Responses could be inhibited by the α 2 ‐adrenoceptor agonist B‐HT920 (3 mg/kg, i.v.) and the μ‐opioid agonist H‐Tyr‐D‐Arg‐Phe‐Lys‐NH 2 (DALDA; 1 mg/kg, i.v.) and the attenuation observed could be overcome by use of the respective antagonists idazoxan (3 mg/kg, i.v.) and naloxone (3 mg/kg, i.v.). 4. Substance P‐induced bronchoconstriction (0.3 μg/kg, i.v.), but not that due to electrical stimulation, was attenuated by indomethacin (3 mg/kg, i.v.), indicating an indirect action of substance P via a product of arachidonic acid metabolism. 5. The prostanoid product of the substance P response was probably thromboxane A 2 . 6. Hence, novel drug development could be directed towards tachykinin receptors or to the synthesis, release and degradation of neuropeptides.