MORPHINE, BUT NOT SODIUM CROMOGLYCATE, MODULATES THE RELEASE OF SUBSTANCE-P FROM CAPSAICIN-SENSITIVE NEURONS IN THE RAT TRACHEA INVITRO

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 nM), capsaicin (100 nM-10-mu-M), and bradykinin (BK; 10 nM-1-mu-M) but not des-Arg9-BK (1-mu-M) stimulated SP-LI release by a calcium-dependent mechanism. 4 SCG (1-mu-M and 100-mu-M) did not affect spontaneous, potassium (60 mM)- or BK (1-mu-M-stimulated SP-LI release. 5 Morphine (0.1-100-mu-M) caused dose-related inhibition of potassium (60 mM)-stimulated SP-LI release with the greatest inhibition of 60.4 +/- 13.7% at 100-mu-M. The effect of morphine was not mimicked by the kappa-opioid receptor agonist, U50,488H (10-mu-M) or the delta-opioid receptor agonist, Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE). 6 The effect of morphine was totally obolished by prior and concomitant exposure to naloxone (100 nM) which had no effect on control release values. 7 We conclude that opioid receptors, predominantly of the mu-opioid receptor subtype, inhibit SP-LI release from PAN in the rat trachea and suggest that centrally inactive mu-opioid receptor agonists may have therapeutic potential in the treatment of asthma.