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 hippocampal interneurones in slices of rat brain tissue in vitro. Bath application of the bombesin-like neuropeptides gastrin-releasing peptide (GRP) or neuromedin B (NMB) produced a large membrane depolarization that was blocked by pre-incubation with the subtype 2 bombesin (BB2) receptor antagonist [D-Phe6, Des-Met14]bombesin-(6-14)ethyl amide. 2. The inward current elicited by NMB or GRP was unaffected by K+ channel blockade 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 magnitude of the GRP-induced current at -60 mV. In contrast, replacement of external NaCl with LiCl had no effect on the magnitude of this current. 4. Photorelease of caged GTPgammaS inside neurones irreversibly potentiated the GRP-induced current at -60 mV. Similarly, bath application of the phospholipase C (PLC) inhibitor U-73122 significantly reduced the size of the inward current induced by GRP. 5. Reverse transcription followed by the polymerase chain reaction using cytoplasm from single hippocampal interneurones demonstrated the expression of BB2 receptor mRNA together with glutamate decarboxylase (GAD67). 6. Although bath application of GRP or NMB had little or no effect on the resting membrane properties of CA1 pyramidal cells per se, these neuropeptides produced a dramatic increase in the number and amplitude of miniature inhibitory postsynaptic currents in these cells in a TTX-sensitive manner.
Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, Robinson Way, Cambridge CB2 2QB, UK.
K
K
Lee
A K
AK
Dixon
I
I
Gonzalez
E B
EB
Stevens
S
S
McNulty
R
R
Oles
P J
PJ
Richardson
R D
RD
Pinnock
L
L
Singh
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D007473:Ion Channels; D010446:Peptide Fragments; D010455:Peptides; D018004:Receptors, Bombesin; C086327:bombesin (6-14)-ethylamide, Phe(6)-des-Met(14)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D010738:Type C Phospholipases; D005968:Glutamate Decarboxylase; D018021:Lithium Chloride; D001839:Bombesin