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

Abstract

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. 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. 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. Photorelease of caged GTPγS 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. 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). 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.

A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory

“…Within the brain, GRPR is highly expressed in the cell bodies and dendrites of neurons in areas including the dorsal hippocampus and lateral amygdala [23]. Hippocampal GRPRs might be activated by the mammalian bombesin-like peptide GRP released from excitatory neurons [14,21]. GRPR activation might in turn lead to activation of intracellular signaling cascades including the phospholipase C/protein kinase C and MAPK pathways [24].…”

“…The GRPR is member of the bombesin-like peptide receptor subfamily of G-protein coupled receptors that is activated by the amphibian peptide bombesin or its mammalian counterpart gastrin-releasing peptide (GRP) (for a recent review, see [20]). In the brain, GRP is proposed to be released from excitatory neurons in brain areas including the dorsal hippocampus and bind to GRPRs expressed on the postsynaptic membrane [14,21]. We have previously shown that systemic administration of the GRPR antagonist [D-Tpi 6 , Leu 13 c(CH 2 NH)-Leu 14 ] bombesin (6-14) (RC-3095) impairs aversive memory without affecting nonaversive memory in rats [17].…”

Role of Calcium in Neurotensin-Evoked Enhancement in Firing in Mesencephalic Dopamine Neurons

“…Previous experiments have revealed that NT increases the firing rate of DAergic neurons by activating nonselective cationic conductances (Seutin et al, 1989;Mercuri et al, 1993;Farkas et al, 1996). In addition to NT receptors, it is known that other G q -coupled receptors can enhance Ca 2ϩ -activated nonselective cationic conductances through an IP 3 -and Ca 2ϩ -dependent signaling pathway Congar et al, 1997;Lee et al, 1999).…”

Effects of gastrin-releasing peptide agonist and antagonist administered to the basolateral nucleus of the amygdala on conditioned fear in the rat

“…Indeed, Shumyatsky et al (2002) demonstrated that GRP receptors are located on GABAergic interneurons within the BLA and that excitation of these interneurons increases inhibition of principle neurons. Similarly, GRP was found to depolarize hippocampal interneurons in vitro, resulting in an increase in frequency and amplitude of spontaneous inhibitory post-synaptic currents (Lee et al 1999), while Andrews et al (2000) showed that GRP increases extracellular levels of GABA in the hippocampus through stimulation of BB 2 receptors. Moreover, Dantas et al (2006) found that, at high doses (10 μg/side), the post-training administration of RC-3095 to the dorsal hippocampus enhanced 24 h memory for inhibitory avoidance training, and this enhancement was prevented by a pretraining infusion of an otherwise inert dose of the GABA A receptor agonist muscimol.…”