Effect of experimental diabetes on GABA-mediated inhibition of neurally induced contractions in rat isolated trachea

1. In the present study, we investigated the effect of GABA and selective G ABA agonists and antagonists on neurally induced tracheal contractions in s treptozotocin (STZ) diabetic rats. 2. Contractile responses to electrical field stimulation (EFS) in rat trach eal rings were completely abolished by atropine and tetrodotoxin, but were unaffected by the ganglion blocker hexamethonium, indicating that they were mediated via neuronal release of acetylcholine (ACh), 3. Contractions induced by EFS, but not by exogenous ACh, were inhibited by GABA and the selective GABAB receptor agonist baclofen, but not by the sel ective GABAA receptor agonist 3-aminopropane sulphonic acid. The inhibitory effects of GABA or baclofen were not affected by the GABAA antagonist bicu cuiline, but were significantly reversed by the GABAB antagonist phaclofen, 4. The inhibitory effects of both GABA and baclofen were found to be signif icantly greater in trachea from control rats compared with tissues from dia betic rats. 5. Non-adrenergic, non-cholinergic relaxation responses elicited by EFS in precontracted tracheal rings from diabetic and control rats were similar in magnitude and were unaffected by GABA or GABA analogues. 6. These results suggest that GABA decreases the response to EFS by directl y inhibiting the evoked release of ACh through GABAB receptors in rat trach ea and that STZ-induced diabetes causes an impairment in the inhibitory eff ect of GABA on neurally induced contractions in this tissue.