Vagal neurotransmission to the ferret lower oesophageal sphincter: inhibition via GABA(B) receptors

1 GABA(B) receptors modulate the function of the lower oesophageal sphincte r (LOS) in vivo by inhibiting neurotransmitter release in the vagal pathway controlling LOS relaxation. We aimed to determine whether this effect was mediated peripherally on vagal motor outflow to the ferret LOS in vitro. 2 The LOS, with intact vagal innervation, was prepared from adult ferrets a nd LOS tension measured. Vagal stimulation (0.5-10 Hz, 30V) evoked a tetrod otoxin-sensitive, frequency dependent relaxation. 3 Both GABA (3 x 10(-4) M) and (+/-)baclofen (2 x 10(-4) M) inhibited vagal ly-stimulated LOS relaxation. The potent GABA, receptor-selective agonist 3 -APPA dose-dependently inhibited vapally-stimulated LOS relaxation, with an EC50 value of 0.7 mu M. 4 Decreased responses following vagal stimulation in the presence of (+/-)b aclofen or 3-APPA were reversed with the potent GABAB receptor antagonist C GP 62349. 5 Neither CGP 62349 nor muscimol (GABA, receptor agonist) alone affected LO S responses following vagal stimulation. 6 Agonists of other G protein-coupled receptors (clonidine (alpha(2)-adreno ceptor) (5 x 10(-6) M), U50488 (kappa opioid) (10(-5) M), neuropeptide Y (1 0(-6) M) did not affect vagally-mediated LOS relaxation. 7 The present study supports a discrete presynaptic inhibitory role for GAB A(B) receptors on vagal preganglionic fibres serving inhibitory motorneuron es in the ferret LOS.