GABA B receptor modulation of 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. 801 - 804
• Main Authors: Ray, N.J., Jones, A.J., Keen, P.
• Format: Journal Article
• Language: English
• Published: 01-04-1991
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1991.tb12255.x

The role of γ‐aminobutyric acid (GABA) as an inhibitory transmitter in the central nervous system is well documented. Recently, GABA
A
and GABA
B
receptors have been identified in the peripheral nervous system, notably on primary afferent neurones (PAN). We have utilised a multi‐superfusion system to investigate the effect of selective GABA receptor agonists and antagonists on the release of substance P (SP) from the rat trachea
in vitro
.
GABA (1–100 μ
m
) did not affect spontaneous release of SP‐like immunoreactivity (LI) but caused dose‐related inhibition of calcium‐dependent potassium (60 m
m
)‐stimulated SP‐LI release. The greatest inhibition of 77.7 ± 18.8% was observed at 100 μ
m
.
The inhibitory effect of GABA was mimicked by the GABA
B
receptor agonist, (±)‐baclofen (1–100 μ
m
), but not the GABA
A
receptor agonist, 3‐amino‐1‐propane‐sulphonic acid (3‐APS, 1–100 μ
m
). Baclofen (100 μ
m
) had no effect on SP‐LI release stimulated by capsaicin (1 μ
m
).
The inhibitory effect of baclofen (30 μ
m
) was significantly reduced by prior and concomitant exposure to the GABA
B
receptor antagonist, phacolofen (100 μ
m
) but not the GABA
A
receptor antagonist, bicuculline (10 μ
m
). Neither antagonist, alone, affected spontaneous or potassium‐stimulated SP‐LI release.
We conclude that activation of pre‐synaptic GABA
B
receptors on the peripheral termini of PANs in the rat trachea inhibits SP‐LI release and suggest that GABA
B
receptor agonists may be of value in the therapeutic treatment of asthma.