Gastrin-releasing peptide receptors in the central nervous system: role in brain function and as a drug target (original) (raw)
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Gastrin-releasing peptide receptor content in human glioma and normal brain
Brain Research Bulletin, 2010
The gastrin-releasing peptide receptor (GRPR) has been put forward as a therapeutic target in brain tumors. Here we evaluated GRPR presence in glioma specimens from patients as well as in normal human brain samples. Sections of paraffin-embedded brain tumors and non-neoplastic control brain tissue were analyzed with immunohistochemistry for GRPR content. Digital image analysis revealed that 100% of glioma samples
Neuropharmacology, 2007
The gastrin-releasing peptide receptor (GRPR) has been implicated in central nervous system (CNS) diseases, including neurodevelopmental disorders associated with autism. In the present study we examined the effects of GRPR blockade during the neonatal period on behavioral measures relevant to animal models of neurodevelopmental disorders. Male Wistar rats were given an intraperitoneal (i.p.) injection of either saline (SAL) or the GRPR antagonist [D-Tpi 6 , Leu 13 psi(CH 2 NH)-Leu 14 ] bombesin (6e14) (RC-3095; 1 or 10 mg/kg) twice daily for 10 days from postnatal days (PN) 1 to 10. Animals treated with RC-3095 showed pronounced deficits in social interaction when tested at PN 30e35 and impaired 24-h retention of memory for both novel object recognition (NOR) and inhibitory avoidance (IA) tasks tested at PN 60e71. Neither shortterm memory tested 1.5 h posttraining nor open field behavior were affected by neonatal GRPR blockade. The implications of the findings for animal models of neurodevelopmental disorders are discussed.
Molecular Pain, 2010
Gastrin-releasing peptide (GRP) has been proposed as a peptidergic molecule for behavioral fear and itching. Immunohistochemistry and in situ hybridization studies have shown that GRP and GRP receptor are widely distributed in forebrain areas. Less information is available for the functional action for GRP in the prefrontal cortex including the anterior cingulate cortex (ACC). Here we used whole-cell patch-clamp recording technique to study the modulation of synaptic transmission by GRP in the ACC. We found that GRP increased the frequency of sIPSCs recorded while had no significant effect on sEPSCs in ACC pyramidal neurons. The facilitatory effect of GRP on sIPSCs was blocked by the GRP receptor antagonist, RC3095. In the presence of TTX, however, GRP had no effect on the mIPSCs. Therefore, activation of GRP receptor may facilitate the excitation of the interneurons and enhanced spontaneous GABAergic, but not glutamatergic neurotransmission. Similar results on GRP modulation of GAB...
Biochemical Pharmacology, 2005
The bombesin (Bn) receptor family includes the gastrin-releasing peptide (GRPR) and neuromedin B (NMBR) receptors, Bn receptor subtype 3 (BRS-3) and Bn receptor subtype 4 (BB 4). They share 50% homology, yet their affinities for gastrin-releasing peptide (GRP) differ. The determinants of GRP high affinity for GRPR and BB 4 , and low affinity for BRS-3 are largely unknown. To address this question we made an analysis of structural homologies in Bn receptor members correlated with their affinities for GRP to develop criteria to identify amino acids important for GRP selectivity. Fourteen differences were identified and each was mutated singly in GRPR to that found in hBRS-3. Eleven mutants had a loss of GRP affinity. Furthermore, three of four amino acids in the GRPR selected used a similar approach and previously reported to be important for high affinity Bn binding, were important for GRP affinity. Some GRPR mutants containing combinations of these mutations had greater decreases in GRP affinity than any single mutation. Particularly important for GRP selectivity were K101, Q121, A198, P199, S293, R288, T297 in GRPR. These results were confirmed by making the reverse mutations in BRS-3 to make GRP gain of affinity mutants. Modeling studies demonstrated a number of the important amino acids had side-chains oriented inward and within 6 Å of the binding pocket. These results demonstrated this approach could identify amino acids needed for GRP affinity and complemented results from chimera/mutagenesis studies by identifying which differences in the extracellular domains of Bn receptors were important for GRP affinity.
Presence of gastrin-releasing peptide in neurons of the geniculate ganglion in rat and man
Neuroscience Letters, 1992
Gastrin-releasmg peptide (GRP) was demonstrated by immunohxstochemlstry and high-performance liquid chromatography to be present m the great majority of neurons in the geniculate ganglion of rat and man. This was in contrast to findings in the sphenopalatme ganglion of rat, where onl~ httle GRP was found, and in the otic, tngeminal, glossopharyngeal-vagal and internal carotid ganglia, where no GRP-containmg cells could be demonstrated. The peptide was not detected by immunohistochem~stry m nerve fibers within structures innervated from the ganglion (tongue, ~oft palate, retroauricular skin and facial musculature). The retrograde axonal tracer True blue accumulated in these neurons of rat after application not only in the tongue and soft palate but also in the retroauricular skin.
Psychopharmacology, 2006
Rationale Bombesin (BB), an amphibian peptide, was shown to affect the expression of the stress response. However, the physiological role of the mammalian counterparts of BB in mediating anxiety and fear responses remain to be characterized. Objective This study examined the effects of gastrinreleasing peptide (GRP), a mammalian analogue of BB, and its receptor antagonist, BW2258U89, on conditioned emotional response (CER), using fear conditioning. Materials and methods The effects of these compounds on contextual and cued fear conditioning were assessed after direct bilateral infusions into the prelimbic (PrL) cortex, infralimbic (IL) cortex or central nucleus of the amygdala (CeA).