GABA(A) receptor-mediated stimulation of non-adrenergic non-cholinergic neurones in the dog ileocolonic junction

Abstract

1. The inhibitory effects of γ-aminobutyric acid (GABA), the GABA(A) receptor agonist homotaurine and the GABA(B) receptor agonist (±)-baclofen were investigated on circular muscle strips of the dog terminal ileum and ileocolonic junctions. 2. In the presence of atropine, GABA and homotaurine induced concentration-dependent relaxations, similar to the non-adrenergic non-cholinergic (NANC)-mediated relaxations evoked by electrical stimulation or by acetylcholine. The ileocolonic junction was more sensitive to GABA and homotaurine than the ileum (±)-Baclofen had no effect. Cross desensitization only occurred between GABA and homotaurine. 3. The GABA(A) receptor antagonist bicuculline shifted the concentration-response curves to GABA and homotaurine to the right. The maximal relaxation to GABA remained unaffected. 4. GABA-induced relaxations were not inhibited by timolol, guanethidine, domperidone, hexamethonium and desensitization to ATP, but were abolished by tetrodotoxin. 5. Bicuculline, and pretreatment with GABA or (±)-baclofen had no effect on the NANC-evoked relaxations to electrical stimulation and acetylcholine. 6. In conclusion, GABA stimulates GABA(A) receptors located on inhibitory NANC neurones in the dog ileocolonic junction. Our results suggest that it is unlikely that GABA is the final inhibitory NANC neurotransmitter.