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1.
Somatostatin receptors in the Rhesus monkey brain: localization and pharmacological characterization
V. Silke Thoss Charles Piwko Daniel Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1996,353(6):648-660
To characterize the nature and distribution of somatostatin (SRIF) receptors, radioligand binding studies and in vitro receptor autoradiography were performed in Rhesus monkey brain using either [125I]LTT-SRIF-28 ([Leu8,D-Trp22,125I-Tyr25]SRIF-28) alone or in the presence of 3 nM seglitide (to block sst2 sites), [1251]Tyr3-octreotide or [125I] CGP 23996 (c[Asu-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) in buffer containing either 120 mM Na+ or 5 mM Mg2+. [125I]Tyr3-octreotide labelled an apparently homogeneous population of sites in cerebral and cerebellar cortex (B
max = 27.3±2.8 fmol/mg protein and 52.6±8.6 fmol/mg protein, pKd = 9.46±0.03 and 9.93±0.03, respectively). The pharmacological profile of these sites correlated highly significantly with that of human recombinant sst2 receptors (r = 0.996), but not or much less with that of human recombinant sst3 and sst5 receptors (r = 0.12 and 0.45, respectively). [125I]CGP 23996 (in Na+-buffer) also labelled an apparently homogeneous population of sites in Rhesus monkey cerebral cortex membranes (B
max = 3.1±0.3 fmol/mg protein, pKd = 10.57±0.08), the pharmacological profile of which was highly significantly correlated with the profiles of human recombinant sst1 and sst4 receptors (r = 0.98 and 0.96, respectively).Using receptor autoradiography, high levels of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide recognition sites were found in basal ganglia, molecular and granular layers of the cerebellum and layers III, V and VI of entorhinal cortex. In these regions, the addition of 3 nM seglitide produced a marked decrease of [125I]LTT-SRIF-28 binding. Low levels of [125I]LTT-SRIF-28 binding were observed in subiculum, pituitary and choroid plexus. By contrast, [125I]CGP 23996 labelling in the presence of Mg2+ as well as Na+ ions was highest in pituitary and choroid plexus. However, [125I]CGP 23996 binding was diversely affected by these ionic conditions in several regions of hippocampus and cerebral cortex. Displacement of [125I]CGP 23996 (in Mg2+-buffer) with seglitide in the molecular layer of the cerebellum, deep layers of the entorhinal cortex, layers I, II and V of the insular cortex and frontal pole yielded complex competition curves suggesting the presence of two populations of SRIF receptors. By contrast, [125I]CGP 23996 binding (in Mg2+-buffer) in the choroid plexus, hilus of the dentate gyrus and stratum oriens and radiatum of the CA3 field of hippocampus was not affected by seglitide up to 10 M, suggesting only sst1 and/or sst4 sites which have a negligible affinity for seglitide to be present in these structures.Taken together, these results suggest that [125I]CGP 23996 (in the presence of Na+) labels exclusively SRIF-2 receptors (sst1 and/or sst4), whereas in the presence of Mg2+ ions, [125I]CGP 23996 labels both SRIF-2 and SRIF-1 receptors (sst2, sst3 and sst5). The present study also demonstrates the presence and differential distribution of sst2 and sst1/sst4 receptors in the Rhesus monkey brain. 相似文献
2.
Charles Piwko V. Silke Thoss Daniel Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(6):607-613
Radioligand binding studies were performed in membranes of rat cerebellum using [125I]-[Tyr3]octreotide ([125I]204-090) to characterize the nature of cerebellar somatostatin receptors. Saturation experiments suggest the presence of a single class of binding sites with high affinity, pKd = 9.53 ± 0.11, but low receptor density, B
max = 12.7 ± 1.0 fmol/mg protein. The pharmacological profile of [125I]204-090 sites in cerebellar membranes was established using a range of ligands known to interact with SSTR-2 (now called sst2) and other somatostatin (SRIF) receptors. SRIF analogues such as octreotide (SMS 201-995), seglitide (MK 678) and somatuline (BIM 23014) displayed very high affinity for cerebellar [125I]204-090 binding sites. The data were compared to results obtained using the same ligand in rat cerebral cortex membranes known to represent sst2 binding. The pharmacological characteristics of the cerebellar sites were in close correlation with those of the cerebral cortex (r = 0.976, n = 19, p < 0.001) and CHO-cells expressing human recombinant sst2 receptor (r = 0.977, n = 19, p < 0.001). By contrast, there was very little correlation between cerebellar binding and published affinities for rat sst5 receptors (r = 0.465), for which octreotide has also high affinity. In vitro autoradiographic studies performed in cerebellar slices using [125I]204-090 demonstrated the presence of binding sites in the molecular layer of the rat cerebellum. In situ hybridization studies using sst2 receptor mRNA selective oligoprobes confirmed the presence of sst2 receptor mRNA in the rat cerebellum. Together, the present data demonstrate the presence of a low density of SRIF receptors in the molecular layer of the adult rat cerebellum which are best characterized as sst2. This is the first pharmacological characterization and localization of sst2 receptors in the adult rat cerebellum. 相似文献
3.
Somatostatin receptors in the ventral pallidum/substantia innominata modulate rat locomotor activity
Rational Somatostatin and its receptors (sst1 and sst2) have been localized in brain nuclei implicated in motor control, such as the nucleus accumbens, ventral pallidum (VP) and
substantia innominata (SI).
Objectives The objective of the study is to investigate the effect of somatostatin and selective sst1 and sst2 analogs infused in the VP/SI on the locomotor activity of the rat.
Methods Somatostatin (15, 30, 60, 120 and 240 ng/0.5 μl/side), CH275 (sst1 analog; 60, 180, 240 and 480 ng/0.5 μl/side), MK678 (sst2 analog; 120, 240 and 480 ng/0.5 μl/side), L-809,087 (sst4 agonist, 240 ng/0.5 μl/side) or saline (vehicle) were infused bilaterally in the VP/SI of the rat and locomotor activity
measured for 60 min. The effect of SRA-880 (sst1 antagonist) and CYN-154806 (sst2 antagonist) on somatostatin-, CH275- and MK678-mediated locomotor activity was also ascertained.
Results Somatostatin decreased locomotor activity in the first 30 min after its infusion in the VP/SI and in a dose-dependent manner.
The sst1 and sst2 antagonists, SRA-880 and CYN-154806, respectively, reversed the somatostatin effect. The sst1 and sst2 agonists CH275 and MK678, respectively, mimicked somatostatin’s actions, while the selective sst4 agonist L-809,087 had no effect. Moreover, SRA-880 and CYN-154806 reversed the respective agonist action on locomotor activity.
Conclusion The present study provides functional evidence for the presence of sst1 and sst2 receptors in the VP/SI and their implication in motor control. The mechanism via which somatostatin and agonists mediate
the attenuation of locomotor activity is presently being investigated. 相似文献
4.
Autoradiographic analysis of somatostatin SRIF1 and SRIF2 receptors in the human brain and pituitary
V. Silke Thoss Charles Piwko Alphonse Probst D. Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(2):168-176
The distribution of somatostatin (SRIF) receptor sites was studied by in vitro receptor autoradiography in the human brain
and pituitary using the SRIF1 (sst2) receptor selective [125I]Tyr3-octreotide, the non-subtype selective [125I]LTT-SRIF-28 ([Leu8,D-Trp22,125I-Tyr25]SRIF-28) and the SRIF2-receptor selective [125I]CGP 23996 (c[Asu-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) in buffer containing 120 mM Na+. SRIF receptor autoradiography was compared with mRNA expression of somatostatin receptors sst1–5 as studied by in situ hybridisation in human brain.
High levels of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide recognition sites were found in the deep layers of cerebral cortex and molecular layer of cerebellum of the human
brain. The hypothalamus, choroid plexus, most areas of the brainstem and dentate nucleus were associated with low levels of
binding. In contrast to [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide, no difference was observed for [125I]CGP 23996 labelling in the various layers of cerebral cortex. The choroid plexus, substantia nigra and molecular layer of
the cerebellum presented high densities of [125I]CGP 23996 binding sites whereas no binding was observed in the hypothalamus and locus coeruleus using this radioligand.
Both lobes of the human pituitary displayed low levels of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide binding. By contrast, the anterior lobe of the pituitary displayed very high levels of [125I]CGP 23996 labelled sites whereas intermediate levels were found in the posterior lobe. There was a partial overlap between
sst2 receptor mRNA and [125I]Tyr3-octreotide binding, although the distribution of the binding sites was much wider than that of receptor mRNA. The same observation
was made for sst1 and/or sst4 receptor mRNA and [125I]CGP 23996 labelled sites.
The present data show that SRIF1 and SRIF2 receptors are present in the human brain with different distributions, especially in the cerebral cortex and the pituitary.
The very similar distribution of sites labelled with [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide suggests (i) that sst2 receptors are predominant within the SRIF1 family in the human brain and (ii) that [125I]LTT-SRIF-28 under the conditions used in the present study, does not significantly label SRIF2 sites.
Received: 8 August 1996 / Accepted: 8 November 1996 相似文献
5.
J. Pérez M. Rigo K. Kaupmann C. Bruns K. Yasuda G. I. Bell H. Lübbert D. Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1994,349(2):145-160
In situ hybridization histochemistry was performed to analyse the distribution of the messenger RNA (mRNA) of three putative somatostatin (SRIF) receptors in rat brain, using oligonucleotide probes derived from the cDNA coding for SSTR-1, SSTR-2, and SSTR-3 receptors.SSTR-1 signals were found in layers VVI of the cerebral cortex, in primary olfactory cortex, taenia tecta, subiculum, entorhinal cortex, granular layer of the dentate gyrus, amygdala and cerebellar nuclei. Signals for SSTR-2 were found in the frontal cerebral cortex (layers IV, V and VI), taenia tecta, claustrum, endopiriform nucleus, locus coeruleus, medial habenula, subiculum, granular cell layer of the dentate gyrus and amygdala. High levels of SSTR-3 hybridization were found in the olfactory bulb, primary olfactory cortex, islands of Calleja, medial habenula, amygdala, granular layer of the dentate gyrus, various thalamic and pontine nuclei and in the granular and Purkinje cell layers of the cerebellum.The distribution of the hybridization signals of the oligoprobes is consistent with the labelling of specific SRIF binding sites in rat brain. Especially, SSTR-2 and SSTR-1 oligos seem to label regions in which SS-1 and SS-2 receptors, respectively, have been previously characterized in autoradiographical studies. The situation is less clear with SSTR-3 mRNA, since SRIF binding in adult rats is usually low or absent in cerebellum, although some cerebellar nuclei appear to be labelled in the adult. The localization of SSTR-1, SSTR-2 and SSTR-3 mRNAs suggests that SRIF receptor subtypes in rat brain show profound differences in their distribution and are involved in a variety of central, in addition to neuroendocrine, functions.Monique Rigo, who contributed very significantly to this work, died tragically on January 21, 1993
Correspondence to: D. Hoyer at the above address 相似文献
6.
p11 is an adaptor protein which binds to serotonin 5-HT1B receptors and 5-HT4 receptors and regulates their localization at the cell surface. In the present study, we examined to what extent p11 containing neurons co-expressed 5-HT1BR and/or 5-HT4R in cerebral cortex, hippocampus, cerebellum and caudate-putamen. A triple-labeling immunohistochemical approach was taken using antibodies to detect native p11 and 5-HT1BR combined with visualization of EGFP driven under the 5-HT4R promoter in BAC-transgenic mice. In the caudate-putamen, the hippocampal pyramidal cell layer of CA1 and the hippocampal granule cell layer of dentate gyrus, most p11 containing cells co-expressed both 5-HT1BR and 5-HT4R. In the cingulate cortex, stratum radiatum/oriens of CA1, hilus of the dentate gyrus and cerebellar cortex, many cells co-expressed p11 and 5-HT1BR, but not 5-HT4R. In the studied brain regions, few cells solely expressed p11 without any significant expression of 5-HT1BR or 5-HT4R. It can be concluded that p11 is anatomically positioned to modulate serotonin neurotransmission, via 5-HT1BR and 5-HT4R, in brain regions important for emotionality, cognition and locomotion. 相似文献
7.
Forbes Alderton Tai-Ping D Fan Marcus Schindler Patrick P A Humphrey 《British journal of pharmacology》1998,125(8):1630-1633
We have investigated the actions of somatostatin (SRIF) and angiopeptin on cell proliferation of CHO-K1 cells expressing the recently cloned rat sst2(b) receptor (CHOsst2(b)) and compared these to their effects in cells expressing the sst2(a) receptor (CHOsst2(a)). In contrast to the sst2(a) receptor, the sst2(b) receptor did not mediate inhibition of bFGF (10 ng ml−1)-stimulated re-growth and cell proliferation. Rather, SRIF (0.1–1000 nM) and angiopeptin (0.1–1000 nM) stimulated basal re-growth and proliferation of CHOsst2(b) cells in a concentration-dependent manner (estimated pEC50 values of 7.8 and 7.9, respectively). The opposite effects of SRIF on cell proliferation mediated through the two sst2 receptor isoforms were both abolished by 18 h pre-treatment with pertussis toxin. The proliferative effect via the sst2(b) receptor was also abolished by the tyrosine kinase inhibitor, genistein. In conclusion, the present study shows that the rat sst2(a) and sst2(b) receptor splice variants mediate opposite effects on cell proliferation. 相似文献
8.
目的观察大鼠电惊厥后脑内生长抑素受体的变化。方法应用受体结合放射自显影术、计算机显微图象处理技术观测。结果正常大鼠大脑皮层、杏仁核、新纹状体、伏膈核、海马CA区、齿状回、嗅球、弓状核、下丘脑室周区、下丘脑腹内侧核、视前区内侧区、中央灰质、黑质等脑区内有125I-Tyr11-SS28特异性结合;电惊厥后,大鼠颞叶听皮质、梨状皮质、内嗅皮质、杏仁内侧核、海马CA区、齿状回、下丘脑腹内侧核等脑区125I-Tyr11-SS28的特异性结合比正常大鼠显著增加(P<0.05)。结论电惊厥的发作可能与不同脑区内生长抑素受体的上调有关。 相似文献
9.
Forbes Alderton Heather Lauder Wasyl Feniuk Tai-Ping D Fan Patrick P A Humphrey 《British journal of pharmacology》1998,124(2):323-330
- Somatostatin (SRIF) exerts antiproliferative effects, and angiopeptin (an sst2/sst5 receptor-selective analogue) has recently been evaluated in clinical trials for the prophylaxis of restenosis following coronary angioplasty. Using an in vitro model of cell growth we have examined the effects of SRIF and angiopeptin on cell proliferation in CHO-K1 cells stably transfected with the human or rat recombinant sst2 or sst5 receptor and compared these with their effects on rat aortic vascular smooth muscle cells (VSMC) expressing endogenous somatostatin receptors.
- In CHO-K1 cells, expressing either human or rat recombinant sst2 or sst5 receptors, or in rat aortic VSMC, SRIF and angiopeptin (0.1–1000 nM) had no effect on basal re-growth of cells into a denuded area of a previously confluent monolayer. In contrast, basic fibroblast growth factor (bFGF, 10 ng ml−1) stimulated re-growth of these cells.
- SRIF (0.1–1000 nM) caused a concentration-dependent inhibition of the bFGF-stimulated re-growth in CHO-K1 cells expressing human sst2 (h sst2) or sst5 (h sst5) receptors (pIC50=8.05±0.03 and 8.56±0.12, respectively). In contrast, angiopeptin (0.1–1000 nM) acted as a partial agonist at the h sst2 receptor (44.6±2.7% inhibition of the bFGF-stimulated re-growth at 100 nM; pIC50=8.69±0.25) but was devoid of any agonist activity at the h sst5 receptor.
- In CHO-K1 cells stably expressing rat recombinant sst2 (r sst2) or sst5 (r sst5) receptors, SRIF (0.1–1000 nM) was able to inhibit the bFGF-stimulated re-growth (pIC50=7.98±24 and 8.50±0.12, respectively). Angiopeptin (0.1–1000 nM) caused a concentration-dependent inhibition of bFGF-stimulated re-growth at the r sst2 receptor (pIC50=8.08±0.24) but acted as a partial agonist at the r sst5 receptor (maximum response=57.7±3.6% inhibition of bFGF-stimulated re-growth at 100 nM; pIC50=8.60±0.16).
- Although angiopeptin was inactive as an agonist at the h sst5 receptor, 100 nM angiopeptin potently antagonized the SRIF-induced inhibition of proliferation in CHO h sst5 (estimated pKB=10.4±0.3). 5-Hydroxytryptamine (0.1 nM–10 μM) also inhibited bFGF-stimulated re-growth (pIC50=8.36±0.11) and angiopeptin had no effect on this response (pKB<7).
- SRIF (0.1–1000 nM) caused a concentration-dependent (pIC50=8.04±0.08) inhibition of bFGF-stimulated re-growth in VSMC, whereas angiopeptin displayed weak agonist activity, only inhibiting bFGF-stimulated re-growth at concentrations greater than 100 nM. Angiopeptin (100 nM) caused a rightward displacement of the concentration-effect curve to SRIF with an estimated pKB value of 7.70±0.12.
- These findings suggest that the low intrinsic activity of angiopeptin at the h sst2 receptor, combined with its lack of agonist activity at the h sst5 receptor, may explain the poor clinical efficacy of angiopeptin in trials for coronary artery restenosis, which contrasts with encouraging data found in equivalent in vivo animal studies.
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11.
Aourz N De Bundel D Stragier B Clinckers R Portelli J Michotte Y Smolders I 《Neuropharmacology》2011,61(8):1327-1333
Somatostatin-14 (SRIF) is a potent anticonvulsant in rodent models of limbic seizures in which the hippocampus is its major site of action. However, the distribution of hippocampal sst receptors and their role in the anticonvulsant effects of SRIF remain controversial. Moreover, striking differences have been described between mice and rats. In rats, sst2 but not sst1 receptors play a critical role in the anticonvulsant effects of SRIF. At present, the role of rat sst3 and sst4 receptors in these anticonvulsive effects remains unknown. Here we demonstrate in vivo anticonvulsive actions of rat hippocampal sst3 and sst4 receptors. Using microdialysis and telemetry-based electroencephalographic recordings we show that intrahippocampal administration of the sst2 agonist L-779,976 (500 nM), the sst3 agonist L-796,778 (100 nM) or the sst4 agonist L-803,087 (100 nM) protects rats against focal pilocarpine-induced seizures. SRIF (1 μM)-, sst3- and sst4-mediated anticonvulsive actions are reversed by the selective sst2 receptor antagonist cyanamid 154806 (100 nM). Moreover, the selective sst3 antagonist SST3-ODN-8 (100 nM) blocks the sst4-mediated anticonvulsant effect. Sst3 antagonism does not reverse the sst2- or SRIF-mediated anticonvulsant effects. Our findings provide the first in vivo evidence for potent anticonvulsive properties of sst3 and sst4 receptors in the rat hippocampus. Nevertheless, selective sst2 receptor antagonism prevented these sst3- or sst4 receptor-mediated anticonvulsant effects, suggesting a functional cooperation with rat hippocampal sst2 receptors. 相似文献
12.
Background and purpose:
Histamine is a modulatory neurotransmitter in the brain. Auto- and hetero-histamine H3 receptors are present in human brain and are potential targets of antipsychotics. These receptors may also display disease-related abnormalities in psychiatric disorders. Here we have assessed how histamine H3 receptors in human brain may be affected in schizophrenia, bipolar disorder, major depression.Experimental approach:
Histamine H3 receptor radioligand binding assays were applied to frozen post-mortem prefrontal and temporal cortical sections and anterior hippocampal sections from subjects with schizophrenia, bipolar disorder, major depression and matched controls.Key results:
Compared with the controls, increased H3 receptor radioligand binding was found in dorsolateral prefrontal cortex of schizophrenic subjects (especially the ones who were treated with atypical antipsychotics), and bipolar subjects with psychotic symptoms. No differences in H3 receptor radioligand binding were found in the temporal cortex. In hippocampal formation of control subjects, H3 receptor radioligand binding was prominent in dentate gyrus, subiculum, entorhinal cortex and parasubiculum. Decreased H3 binding was found in the CA4 area of bipolar subjects. Decreased H3 binding in CA2 and presubiculum of medication-free bipolar subjects was also seen.Conclusions and implications:
The results suggest that histamine H3 receptors in the prefrontal cortex take part in the modulation of cognition, which is impaired in schizophrenic subjects and bipolar subjects with psychotic symptoms. Histamine H3 receptors probably regulate connections between hippocampus and various cortical and subcortical regions and could also be involved in the neuropathology of schizophrenia and bipolar disorder. 相似文献13.
Hirotoshi Akane Fumiyo Saito Ayako Shiraki Masahiro Takeyoshi Nobuya Imatanaka Megu Itahashi Tomoaki Murakami Makoto Shibutani 《Toxicology and applied pharmacology》2014
We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc+ neurons at 1000 ppm and Fos+ neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. 相似文献
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Quantitative receptor autoradiography has been employed to determine the binding distribution of [3H]SR 95531 (2'-(3'-carboxy-2',3'-propyl)-3-amino-6-p-methoxyphenylpyrazinium bromide), a GABAA receptor antagonist, in the rat brain. The location showed good correspondence, in most areas, with the binding of [3H]GABA to GABAA receptors. The major exceptions were binding to cerebellum and hippocampus. We also describe here a non-GABA-associated [3H]SR 95531 binding site which is found at its highest level in the hippocampal CA1 region but also in CA2, CA3, dentate gyrus and cerebral cortex. The results support the localisation of [3H]SR 95531 sites to the GABAA receptor complex. 相似文献
16.
Lucaites VL Krushinski JH Schaus JM Audia JE Nelson DL 《Naunyn-Schmiedeberg's archives of pharmacology》2005,371(3):178-184
LY334370 is a high affinity, selective agonist at the 5-HT1F receptor. On this basis, the tritiated compound was examined for its utility in autoradiography to localize the 5-HT1F receptor in rat and guinea pig brain regions. Specific 5-HT1F receptor binding in rat brain was found in layers 4–5 of all cortical regions examined, as well as olfactory bulb and tubercle, nucleus accumbens, caudate putamen, parafascicular nucleus of the thalamus, medial mammillary nucleus, the CA3 region of the hippocampus, subiculum, and several amygdaloid nuclei. In guinea pig brain, the [3H]LY334370 binding sites were found at highest density in claustrum, but also in a layer of the cortex, caudate putamen, nucleus accumbens, thalamus, and medial mammillary nucleus. Some species differences in the distribution of the 5-HT1F receptor were noted. Side by side comparison of rat brain autoradiography with [3H]LY334370 and [3H]sumatriptan showed labeling in the same brain regions. Preliminary binding studies in rhesus monkey and human brain sections showed [3H]LY334370 binding in cortical layers 4–5, subiculum (in the monkey), and the granule cell layer of the cerebellum. These findings suggest a discrete localization of the 5-HT1F receptor in the rat, guinea pig, monkey and human brain, and confirms the utility of [3H]LY334370 as a potential tool to explore further the localization and possible functions of the 5-HT1F receptor. 相似文献
17.
Maternal exposure to 3,3’‐iminodipropionitrile targets late‐stage differentiation of hippocampal granule cell lineages to affect brain‐derived neurotrophic factor signaling and interneuron subpopulations in rat offspring
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Megu Itahashi Hajime Abe Takeshi Tanaka Sayaka Mizukami Yoh Kikuchihara Toshinori Yoshida Makoto Shibutani 《Journal of applied toxicology : JAT》2015,35(8):884-894
3,3’‐Iminodipropionitrile (IDPN) causes neurofilament (NF)‐filled swellings in the proximal segments of many large‐caliber myelinated axons. This study investigated the effect of maternal exposure to IDPN on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 67 or 200 ppm IDPN in drinking water from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, female offspring subjected to analysis had decreased parvalbumin+, reelin+ and phospho‐TrkB+ interneurons in the dentate hilus at 200 ppm and increased granule cell populations expressing immediate‐early gene products, Arc or c‐Fos, at ≥ 67 ppm. mRNA expression in the dentate gyrus examined at 200 ppm decreased with brain‐derived neurotrophic factor (Bdnf) and very low density lipoprotein receptor. Immunoreactivity for phosphorylated NF heavy polypeptide decreased in the molecular layer of the dentate gyrus and the stratum radiatum of the cornu ammonis (CA) 3, portions showing axonal projections from mossy cells and pyramidal neurons, at 200 ppm on PND 21, whereas immunoreactivity for synaptophysin was unchanged in the dentate gyrus. Observed changes all disappeared on PND 77. There were no fluctuations in the numbers of apoptotic cells, proliferating cells and subpopulations of granule cell lineage in the subgranular zone on PND 21 and PND 77. Thus, maternal IDPN exposure may reversibly affect late‐stage differentiation of granule cell lineages involving neuronal plasticity as evident by immediate‐early gene responses to cause BDNF downregulation resulting in a reduction in parvalbumin+ or reelin+ interneurons and suppression of axonal plasticity in the mossy cells and CA3 pyramidal neurons. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Shirayama Y Hashimoto K Iyo M Watanabe K Higuchi T Minabe Y 《European journal of pharmacology》2000,402(3):215-222
Using in situ hybridization and immunohistochemical techniques, we examined the expression pattern of egr-1 mRNA and Egr-1 protein in several brain regions following administration of 3, 4-methylenedioxymethamphetamine (MDMA). Furthermore, we also studied the role of N-methyl-D-aspartate (NMDA) receptor, dopamine D(1) receptor, 5-hydroxytryptamine (5-HT) transporter or 5-HT(2A) receptor in the induction of egr-1 mRNA by MDMA. Basal constitutive levels of egr-1 mRNA were detected in control rat brains. A single administration of MDMA (10 mg/kg) caused marked induction of egr-1 mRNA in the prefrontal cortex, striatum and hippocampal dentate gyrus. However, no changes in the egr-1 mRNA levels were detected in the CA1 region of hippocampus and occipital cortex after administration of MDMA (10 mg/kg). Furthermore, the expression of egr-1 mRNA in the prefrontal cortex, striatum and hippocampal dentate gyrus after administration of MDMA (10 mg/kg) was blocked significantly by pretreatment with NMDA receptor antagonist (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]-cyclohepten-5, 10-imine ((+)-MK801; 1 mg/kg), dopamine D(1) receptor antagonist SCH 23390 (1 mg/kg) or 5-HT uptake inhibitor paroxetine (5 mg/kg), but not by 5-HT(2A) receptor antagonist SR46349B (5 mg/kg). However, high basal levels of Egr-1 immunoreactivity in the rat brain were not altered by administration of MDMA (10 mg/kg). These results suggest that MDMA alters the expression of egr-1 mRNA in several regions of rat brain, and that the expression of egr-1 mRNA by MDMA in the prefrontal cortex, striatum and hippocampal dentate gyrus appears to be mediated, at least in part, by NMDA receptor, dopamine D(1) receptor and 5-HT transporter. 相似文献
20.
N Yang SM Liu LF Zheng T Ji Y Li XL Mi H Xue W Ren JD Xu XH Zhang LS Li Y Zhang JX Zhu 《British journal of pharmacology》2010,159(8):1623-1625