GABAA 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 junction. 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.