Bombesin-like peptides depolarize rat hippocampal interneurones through interaction with subtype 2 bombesin receptors

1. Whole-cell patch-clamp recordings were made from visually identified hip pocampal interneurones in slices of rat, brain tissue in vitro. Bath applic ation of the bombesin-like neuropeptides gastrin-releasing peptide (GRP) or neuromedin B (NMB) produced a large membrane depolarization that was block ed by pre-incubation with the subtype 2 bombesin (BB2) receptor antagonist [D-Phe(6),Des-Met(14)]bombesin-(6-14)ethyl amide. 2. The inward current elicited by NMB or GRP was unaffected by K+ channel b lockade with external Ba2+ or by replacement of potassium gluconate in the electrode solution with caesium acetate. 3. Replacement of external NaCl with Tris-HCl significantly reduced the mag nitude of the GRP-induced current at -60 mV. In contrast, replacement of ex ternal NaCl with LiCl had no effect on the magnitude of this current. 4. Photorelease of caged GTP gamma S inside neurones irreversibly potentiat ed the GRP-induced current at -60 mV. Similarly, bath application of the ph ospholipase C (PLC) inhibiter U-73122 significantly reduced the size of the inward current induced by GRP. 5. Reverse transcription followed by the polymerase chain reaction using cy toplasm from single hippocampal interneurones demonstrated the expression o f BE, receptor mRNA together with glutamate decarboxylase (GAD67). 6. Although bath application of GRP or NMB bad little or no effect on the r esting membrane properties of CAl pyramidal cells per se, these neuropeptid es produced a dramatic increase in the number and amplitude of miniature in hibitory postsynaptic currents in these cells in a TTX-sensitive manner.