GABA-B RECEPTOR MODULATION OF THE RELEASE OF SUBSTANCE-P FROM CAPSAICIN-SENSITIVE NEURONS IN THE RAT TRACHEA INVITRO

1 The role of gamma-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. 2 GABA (1-100-mu-M) did not affect spontaneous release of SP-like immunoreactivity (LI) but caused dose-related inhibitio of calcium-dependent potassium (60 mM)-stimulated SP-LI release. The greatest inhibition of 77.7 +/- 18.8% was observed at 100-mu-M. 3 The inhibitory effect of GABA was mimicked by the GABA(B) receptor agonist, (+/-)-baclofen (1-100-mu-M), but not the GABA(A) receptor agonist, 3-amino-1-propane-sulphonic acid (3-APS, 1-100-mu-M). Baclofen (100-mu-M) had no effect on SP-LI release stimulated by capsaicin (1-mu-M). 4 The inhibitory effect of baclofen (30-mu-M) was significantly reduced by prior and concomitant exposure to the GABA(B) receptor antagonist, phacolofen (100-mu-M) but not the GABA(A) receptor antagonist, bicuculline (10-mu-M). Neither antagonist, alone, affected spontaneous or potassium-stimulated SP-LI release. 5 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.