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Morphine, but not sodium cromoglycate, modulates the release of substance P from capsaicin‐sensitive neurones in the rat trachea in vitro
Author(s) -
Ray N.J.,
Jones A.J.,
Keen P.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12254.x
Subject(s) - substance p , capsaicin , chemistry , morphine , agonist , opioid , endocrinology , (+) naloxone , medicine , pharmacology , bradykinin , opioid receptor , receptor , neuropeptide , biochemistry
1 Opioids have been shown to inhibit substance P (SP) release from primary afferent neurones (PAN). In addition, opioid receptors have been identified on PAN of the vagus nerves. Sodium cromoglycate (SCG) decreases the excitability of C‐fibres in the lung of the dog in vivo . We have utilised a multi‐superfusion system to investigate the effect of opioids and SCG on the release of SP from the rat trachea in vitro . 2 Pretreatment of newborn rats with capsaicin (50 mg kg −1 s.c. at day 1 and 2 of life) resulted in a 93.2 ± 6.3% reduction in tracheal substance P‐like immunoreactivity (SP‐LI) content when determined by radioimmunoassay in the adult. 3 Exposure to isotonically elevated potassium concentrations (37–90 m m ), capsaicin (100 n m –10 μ m ), and bradykinin (BK; 10 n m –1 μ m ) but not des‐Arg 9 ‐BK (1 μ m ) stimulated SP‐LI release by a calcium‐dependent mechanism. 4 SCG (1 μ m and 100 μ m ) did not affect spontaneous, potassium (60 m m )‐ or BK (1 μ m )‐stimulated SP‐LI release. 5 Morphine (0.1–100 μ m ) caused dose‐related inhibition of potassium (60 m m )‐stimulated SP‐LI release with the greatest inhibition of 60.4 ± 13.7% at 100 μ m . The effect of morphine was not mimicked by the κ‐opioid receptor agonist, U50,488H (10 μ m ) or the ω‐opioid receptor agonist, Tyr‐( d ‐Pen)‐Gly‐Phe‐( d ‐Pen) (DPDPE). 6 The effect of morphine was totally abolished by prior and concomitant exposure to naloxone (100 n m ) which had no effect on control release values. 7 We conclude that opioid receptors, predominantly of the μ‐opioid receptor subtype, inhibit SP‐LI release from PAN in the rat trachea and suggest that centrally inactive μ‐opioid receptor agonists may have therapeutic potential in the treatment of asthma.