Morphine, but not sodium cromoglycate, modulates the release of substance P from capsaicin‐sensitive neurones in the rat trachea in vitro

• Published in: British journal of pharmacology Vol. 102; no. 4; pp. 797 - 800
• Main Authors: Ray, N.J., Jones, A.J., Keen, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-1991; Nature Publishing
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Biological and medical sciences; Bradykinin - pharmacology; Capsaicin - pharmacology; Cromolyn Sodium - pharmacology; Enkephalin, D-Penicillamine (2,5); Enkephalins - pharmacology; In Vitro Techniques; Male; Medical sciences; Morphine; Morphine - pharmacology; Muscle, Smooth - innervation; Muscle, Smooth - metabolism; Naloxone - pharmacology; Neurons - drug effects; Neurons - metabolism; Pharmacology. Drug treatments; Potassium Chloride - pharmacology; primary afferent neurone; Pyrrolidines - pharmacology; Rats; Rats, Inbred Strains; Respiratory system; sodium cromoglycate; Substance P - immunology; Substance P - metabolism; Trachea - innervation; Trachea - metabolism; trachea substance P; Agonist; Rat; Substance P; Rodentia; Opiates; In vitro; Opiate receptor; Vertebrata; Mammalia; Animal; Sensitive nerve fiber; Trachea; Release
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1991.tb12254.x

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 mm), capsaicin (100 nm–10 μm), and bradykinin (BK; 10 nm–1 μm) but not des‐Arg9‐BK (1 μm) stimulated SP‐LI release by a calcium‐dependent mechanism.
4
SCG (1 μm and 100 μm) did not affect spontaneous, potassium (60 mm)‐ or BK (1 μm)‐stimulated SP‐LI release.
5
Morphine (0.1–100 μm) caused dose‐related inhibition of potassium (60 mm)‐stimulated SP‐LI release with the greatest inhibition of 60.4 ± 13.7% at 100 μm. The effect of morphine was not mimicked by the κ‐opioid receptor agonist, U50,488H (10 μm) 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 nm) 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.