Bombesin facilitates GABAergic transmission and depresses epileptiform activity in the entorhinal cortex

Bombesin and the bombesin-like peptides including neuromedin B (NMB) and gastrin-releasing peptide (GRP) are important neuromodulators in the brain. We studied their effects on GABAergic transmission and epileptiform activity in the entorhinal cortex (EC). Bath application of bombesin concentration-dependently increased both the frequency and amplitude of sIPSCs recorded from the principal neurons in the EC. Application of NMB and GRP exerted the same effects as bombesin. Bombesin had no effects on mIPSCs recorded in the presence of TTX but slightly depressed the evoked IPSCs. Omission of extracellular Ca(2+) or inclusion of voltage-gated Ca(2+) channel blockers, Cd(2+) and Ni(2+), blocked bombesin-induced increases in sIPSCs suggesting that bombesin increases GABA release via facilitating extracellular Ca(2+) influx. Bombesin induced membrane depolarization and slightly increased the input resistance of GABAergic interneurons recorded from layer III of the EC. The action potential firing frequency of the interneurons was also increased by bombesin. Bombesin-mediated depolarization of interneurons was unlikely to be mediated by the opening of a cationic conductance but due to the inhibition of inward rectifier K(+) channels. Bath application of bombesin, NMB and GRP depressed the frequency of the epileptiform activity elicited by deprivation of Mg(2+) from the extracellular solution suggesting that bombesin and the bombesin-like peptides have antiepileptic effects in the brain.