共查询到20条相似文献,搜索用时 15 毫秒
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Robin V. Searles Mi-Jeong Yoo Ju-Ren He Wei-bin Shen Michael Selmanoff 《Brain research》2000,878(1-2)
GABAergic neurons are estimated to make up more than half of the neuronal population of the hypothalamus and they likely account for some of the structural and functional sexual dimorphisms observed in the mammalian brain. We previously reported sex differences in the rate of GABA turnover in discrete hypothalamic structures of adult rats. In the present study, we extended our search for sex differences in GABA turnover to additional structures, and further determined whether these differences were associated with differences in GAD65 and or GAD67 mRNA levels. Utilizing the GABA transaminase inhibition method, we determined GABA turnover in 14 microdissected brain regions. The rate of GABA turnover was about 2-fold greater in male than in diestrous day one (D1) female rats in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis [DBB(ovlt)], anteroventral periventricular nucleus (AVPv), median eminence (ME), and dorsomedial portion of the ventromedial nucleus (VMNdm). A sex difference also was noted in the DBB(ovlt) for GAD65 mRNA determined by microlysate RNase protection assay. Here, GAD65 levels were almost 2-fold greater in male rats, which suggests that differences in the activity of this GAD enzyme isoform contributes to the difference in turnover in this area. Additionally, in the dorsomedial nucleus (DMN), the GAD65 mRNA level was significantly higher in female rats, and in the medial amygdaloid nucleus (Am), GAD67 mRNA was higher in male rats. These data reveal striking sexual dimorphisms in the rate of GABA turnover and in GAD mRNA levels in specific populations of hypothalamic GABAergic neurons. The functional relationships between these GABAergic neurons and sexually dimorphic phenotypes associated with these structures, such as gonadotropin secretion, reproductive behaviors, seizure threshold and others, warrant further investigation. 相似文献
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Previous in vivo magnetic resonance spectroscopy (MRS) studies of gamma-aminobutyric acid (GABA) synthesis have relied on 13C label incorporation into GABA C2 from [1-13C] or [1,6-13C2]glucose. In this study, the [13C]GABA C1 signal at 182.3 ppm in the carboxylic/amide spectral region of localized in vivo 13C spectra was detected. GABA-transaminase of rat brain was inhibited by administration of gabaculine after pre-labeling of GABA C1 and its metabolic precursors with exogenous [2,5-13C2]glucose. A subsequent isotope chase experiment was performed by infusing unlabeled glucose, which revealed a markedly slow change in the labeling of GABA C1 accompanying the blockade of the GABA shunt. This slow labeling of GABA at elevated GABA concentration was attributed to the relatively small intercompartmental GABA-glutamine cycling flux that constitutes the main route of 13C label loss during the isotope chase. Because this study showed that using low RF power broadband stochastic proton decoupling is feasible at very high field strength, it has important implications for the development of carboxylic/amide 13C MRS methods to study brain metabolism and neurotransmission in human subjects at high magnetic fields. 相似文献
4.
The spin Hamiltonian parameters (zero-field splittings D, g factors g// and g⊥, the hyperfine structure constants and the spin–lattice coupling coefficients |G–|, |G15|, |G51| and |G44|) for V3+ and Cr4+ in α-Al2O3 are theoretically investigated from the perturbation formulas of these parameters for a 3d2 ion under trigonally distorted octahedra. In these formulas, the contributions from the dynamical Jahn–Teller effect, the configuration interactions and the ligand orbital and spin–orbit coupling interactions are quantitatively taken into account in a uniform way based on the ligand field model. The impurity-ligand bond angles related to the C3 axis are found to experience the variations of about 1.5–1.9° due to the dynamical Jahn–Teller nature, yielding more regular octahedra around the 3d2 impurities. In addition, the size mismatching substitution of the smaller host Al3+ by the larger impurities may also bring forward some contributions to the local angular distortions. All the calculated spin Hamiltonian parameters based on the above angular variations show reasonable agreement with the experimental data for both centers. The improvements are achieved in this work by adopting the uniform model and formulas and much fewer adjustable parameters as compared with the previous treatments. 相似文献
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In rabbits the third cerebral ventricle was perfused using a push-pull cannula. Prostaglandin E2 concentration in the perfusate was measured by radioimmunoassay. Prostaglandin concentration rose during fever induced by an intraventricular injection of endogenous pyrogen. Both fever and the increased prostaglandin concentration were suppressed by the intraventricular injection of 100 micrograms of the protein synthesis inhibitor, anisomycin. A possible interpretation of the findings is that anisomycin inhibits the formation of phospholipase A2. If this is true, the implication is that phospholipase A2 has a rapid turnover in brain. 相似文献
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Hiroo Kuroda David S. Baskin Tohru Matsui Horace H. Loh Yoshio Hosobuchi Nancy M. Lee 《Brain research》1986,379(1):68-74
We previously reported that the opioid peptide dynorphin1-13 improves survival chances in stroked cats. Some evidence also suggests that changes in dopamine and gamma-aminobutyric acid (GABA) uptake may be associated with stroke. In the present study, therefore, we determined binding of the opiate [3H]ethylketocyclazocine (EKC), as well as dopamine and GABA uptake in various brain regions of control, stroked and dynorphin1-13-treated stroked cats. Cats were stroked by middle cerebral artery occlusion. In the EKC binding study, the Kd of the high-affinity site of the occluded cortex was significantly increased, relative to that of both the unoccluded side and control cortex. Dynorphin1-13 treatment reversed this effect, lowering the Kd to control level. In the dopamine uptake study, the Km was decreased and Vmax was increased significantly in unoccluded cortex, compared with that in the occluded cortex or in control cortex. Again, dynorphin1-13 reversed these effects, raising the Km and lowering the Vmax. However, the Km of occluded cortex was also increased so that it became significantly higher than that of control cortex. The Km of unoccluded subcortex in stroked cats treated with dynorphin1-13 was significantly reduced compared with control. In the GABA uptake study, there was no significant change in any parameter. The change in opioid binding observed here and its reversal by dynorphin1-13 are consistent with the notion that the peptide's beneficial effect on stroke is mediated through opiate receptors. Since opioid systems in the brain are known to have association with dopaminergic ones, the change in dopamine uptake could also be the result of an opioid effect. 相似文献
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Nociceptin or orphanin FQ (N/OFQ) is the natural ligand of the opioid receptor-like 1 receptor (ORL-1), which has been also classified as the fourth member of the opioid family of receptors and named OP4. Elucidation of the biological role of N/OFQ has been hampered by the lack of compounds that selectively block the OP4 receptor. Recently, a N/OFQ derivative, [Nphe1]N/OFQ(1-13)NH2, has been found to possess OP4 antagonistic properties both in vitro and in vivo models. We investigated its spinal effect in the chronic constriction injury of the sciatic nerve in the rat, a model relevant to neuropathic pain in humans. Intrathecal (i.t.) administration of N/OFQ (0.2–20 nmoles) dose-dependently reversed mechanical allodynic-like behavior, while [Nphe1]N/OFQ(1-13)NH2 (20–120 nmoles, i.t.) was ineffective on its own. [Nphe1]N/OFQ(1-13)NH2 (60–120 nmoles, i.t.) antagonized N/OFQ (about 80% of reduction) but did not modify the activity of morphine (20 nmoles, i.t.). These results further support, for the first time in a chronic model of pain, the specific antagonistic profile of [Nphe1]N/OFQ(1-13)NH2vs the OP4 receptor. This pseudopeptide is an interesting pharmacological tool to better clarify the role of N/OFQ in pathophysiology. 相似文献
8.
Javier Garzn Pilar Snchez-Blzquez John Gerhart Horace H. Loh Nancy M. Lee 《Brain research》1984,302(2)
Dynorphin1–13 is a potent inhibitor of electrically-induced contractions in the guinea pig ileum, where it has the properties of κ-(ethylketocyclazocine) type opioids. In the brain, however, it has no analgesic potency, yet inhibits that induced by morphine. To gain further insight into its mechanism of action in the latter system, we tested its ability to complete for the binding of several opiates to brain membranes in vitro. Dynorphin1–13 inhibited the binding of all ligands examined, including dihydromorphine, d-Ala2-d-Leu5-enkephalin, ethylketacyclazocine (EKC) and naloxone. In all cases, it reduced the number of high affinity sites and, in the case of EKC, it also increased the Kd. We conclude that the mechanism of dynorphin inhibition is not simple rapidly reversible competition and is certainly not identical with respect to all opiate ligands. 相似文献
9.
Nociceptin, also known as orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like1 (ORL1) receptor, is moderately expressed in the hypothalamic paraventricular nucleus (PVN) involved in the integrative control of the function of the endocrine and autonomic nervous systems. Our previous study demonstrated that intracerebroventricular administration of N/OFQ elicits an inhibitory action on the function of the cardiovascular and sympathetic nervous systems in conscious rats. However, the effects of N/OFQ on PVN neurons have not been examined. We investigated the effects of N/OFQ on PVN neurons using a whole-cell patch-clamp recording technique in rat brain slices. N/OFQ (30–1000 nM) hyperpolarized membrane potentials in type 1 and type 2 neurons of the PVN classified by the electrophysiological property. [Phe1ψ(CH2-NH)Gly2]nociceptin(1-13)NH2 (Pheψ) (1–9 μM), a presumed competitive antagonist of the ORL1 receptor, also hyperpolarized membrane potential in both types of neurons. In voltage clamp studies, N/OFQ (3–3000 nM) activated a K+ current concentration-dependently in 69.7% of PVN neurons with an EC50 of 72.4±12 nM. Pheψ (100–9000 nM) also activated a K+ current with an EC50 of 818±162 nM in PVN neurons, and significantly reduced the amplitude of the N/OFQ-stimulated current. The N/OFQ-induced current was not antagonized by the classical opioid receptor antagonist naloxone and putative antagonist nocistatin. These findings suggest that N/OFQ may have a functional role in the PVN. 相似文献
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Protective doses of bovine P2 protein (5, 15 or 50 μg) in incomplete Freund's adjuvant (IFA) were administered to Lewis rats and were followed 2,4 or 10 weeks later by challenging doses of either 250 μg bovine P2 or 2.5 mg bovine PNS myelin in complete Freund's adjuvant (CFA). Protection from experimental allergic neuritis (EAN) could be achieved with a single dose of 5 μg of P2 in IFA. There was little difference between prophylactic 5 μg and 15 μg doses of P2. The degree of protection depended upon the interval between protective innoculation and challenge. Protection was partial at 2 weeks and maximal at 4 weeks at which time there was complete protection against P2-induced EAN and less complete protection from myelin-induced disease. Complete protection at 4 weeks from myelin-induced EAN was achieved with a 50 μg dose. Protection lasted for at least 10 weeks (the longest interval assessed) and was complete with respect to P2-induced EAN. Partial protection was observed in myelin-challenged animals after 10 weeks with the level of protection greater than that observed after 2 weeks. 相似文献
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The regional distribution of D1 dopamine (DA) receptors in the rat brain has been studied by quantitative autoradiography using the specific D1 antagonist [3H]SCH 23390 as a ligand. The binding of [3H]SCH 23390 to striatal sections was saturable, stereospecific, reversible and of high affinity (Kd = 2.05nM); it occurred at single population of sites and possessed the pharmacological features of the D1 DA receptor. The highest densities of [3H]SCH 23390 binding sites were found in the caudate-putamen, olfactory tubercle, nucleus accumbens and substantia nigra (especially in the pars compacta). High densities were also observed in the nucleus interstitialis striae terminalis, the anterior olfactory nucleus, the entopeduncular nucleus, the subthalamic nucleus, the claustrum and the amygdalohippocampal area. An intermediate labelling was found in the anteromedial and suprarhinal DA terminal fields of the cerebral cortex, the basolateral, medial and lateral amygdaloid nuclei, the endopiriform nucleus, the primary olfactory cortex, the globus pallidus, the superior colliculus (especially the superficial layer), the nucleus amygdaloideus corticalis and the dorsal hippocampus (molecular layer of the CA1 and dentate gyrus). In the anteromedial and suprarhinal cortices, [3H]SCH 23390 binding was more concentrated in layers V and VI. Moderate levels of [3H]SCH 23390 were found in the thalamus, hypothalamus, the habenula, the ventral tegmental area, the posterior cingulate and entorhinal cortices, the supragenual dopamine terminal system and the cerebellum (molecular layer). This regional distribution of [3H]SCH 23390 closely correlated (except for the cerebellum) with the reported distribution of dopaminergic terminals. The topographical distribution of [3H]SCH 23390 has also been studied in detail in striatal subregions. The density of D1 receptors was much greater in the ventrolateral sector and medial margin of the striatum than in the ventromedial and dorsolateral sectors. A rostrocaudal decrease in the densities of D1 sites was also found along the rostrocaudal axis of the caudate-putamen. These lateral to medial and anteroposterior gradients overlapped with the density of the dopaminergic afferents. 相似文献
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The potential heterogeneity in the allosteric coupling between GABA and ω1 binding sites within the native GABAA receptor complex has been evaluated in the rat by measuring the enhancement by GABA of [3H]zolpidem binding to ω1 site in membranes from three rat brain structures (neocortex, cerebellum and hippocampus) and brain sections. The maximal stimulatory effect of GABA was significantly higher (265 ± 47%) in cortical membranes than in cerebellar (165 ± 48%) or in hippocampal (118 ± 17%) membranes. These differences are not due either to the presence of different amounts of residual GABA in the membrane preparations or to the labeling, in presence of GABA, of binding sites other than ω1 since: (1) the pharmacological properties of the [3H]zolpidem binding sites were similar in the three regions; (2) the degree of allosteric enhancement was unrelated to the relative proportion of ω1 sites in each structure; and (3) GABA did not increase the Bmax for [3H]zolpidem. Regional differences in the effect of 100 μM GABA on [3H]zolpidem binding were also observed by quantitative autoradiography. Regions where the strongest (3–4-fold) effects of GABA in [3H]zolpidem binding were observed included the substantia nigra, lateral geniculate body, olfactory tubercule and red nucleus. A large increase in [3H]zolpidem binding was also demonstrated in the cingulate and frontoparietal cortices with higher effects in deep (4.2-fold) rather than in superficial layers (3.3-fold). Heterogeneous subregional increases in [3H]zolpidem binding in the presence of GABA were quantified within the cerebellum, hippocampus and superior colliculus. In the cerebellum the effect of this neurotransmitter was larger in the molecular (3.8-fold) than in the granular (2.2-fold) layer. In the hippocampus the effect of GABA was also heterogeneous with larger increases in CA1 and CA2 fields (3.5-fold) than in CA3 field (2.2-fold) and dentate gyrus (2.5-fold). Finally in the deep layers of the superior colliculus GABA stimulation of [3H]zolpidem binding was greater than the superficial layer. In the other structures examined the GABA-induced increase in [3H]zolpidem binding was less than 3-fold. The smallest stimulations were quantified in the entorhinal cortex (2.1-fold), amygdala (2.4-fold) and nucleus accumbens (1.7-fold). These results suggest that [3H]zolpidem sites are associated to, at least, two GABAA receptor subtypes that can be differentiated by their allosteric interaction between GABA and [3H]zolpidem sites. 相似文献
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Weirong Fang Jie Wei Dan Han Xi Chen Guangwei He Qiang Wu Shaoxing Chu Yunman Li 《Thrombosis research》2014
Introduction
Thromboxane A2 (TXA2) induces platelet aggregation and vasoconstriction, and agents that inhibit TXA2 production or interaction with receptors may exert potential application in stroke therapy.Aim
To illustrate the platelet aggregation antagonistic and endothelial protective effect of (E) - 3 - (3 - methoxy - 4 - ((3, 5, 6 - trimethylpyrazin - 2 - yl) methoxy) phenyl) sodium acrylate (MC-002) through TXA2 inhibition and underline mechanisms.Materials and methods
Platelets aggregation and thoracic aorta ring contraction of rabbits were induced by U46619. Human umbilical vein endothelial cells (HUVECs) were further applied to explore the protective effect of MC-002 on endothelium when exposed to tumor necrosis factor - α (TNF-α). MTT method was used to assess cell damage, and ELISA analysis was exerted to estimate nitrogen monoxide (NO), endothelin-1 (ET-1), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) releasing. Fluorescence spectrophotometry was conducted to determine intracellular calcium concentration ([Ca2 +]i), and western blotting method was applied to evaluate the protein expressions of intracellular adhesion molecule-1 (ICAM-1), P-selectin and nuclear factor-kappa B (NF-κB).Results and conclusions
TXA2 analog U46619 mediated obvious platelet aggregation and vasoconstriction. MC-002 inhibited platelet aggregation through administration in vivo and incubation with platelet in vitro, and relaxed aorta ring in endothelium dependent manner. MC-002 alleviated cell damage, [Ca2 +]i overload, ET-1 overexcretion and TXB2 activation, but improved NO availability reduction in HUVECs treated with TNF-α. Furthermore, MC-002 downregulated ICAM-1, P-selectin and NF-κB overexpression induced by TNF-α. In conclusion, MC-002 exerted antiplatelet aggregation effect through TXA2 inhibition and relieved inflammatory injury of endothelial cells through NF-κB signal pathway. 相似文献15.
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Takatoshi Mochizuki Frank P. Jansen Rob Leurs Albert D. Windhorst Atsushi Yamatodani Kazutaka Maeyama Hendrik Timmerman 《Brain research》1996,743(1-2)
We investigated the brain penetration of the histamine H3 receptor antagonists thioperamide and clobenpropit using ex vivo [125I]iodophenpropit binding. Homogenates of the rat cortex, striatum and mouse whole brain were prepared 1 h after subcutaneous injection of the H3 antagonists and incubated with [125I]iodophenpropit, a radiolabeled H3 receptor antagonist, to determine the H3 receptor occupancy. Specific [125I]iodophenpropit binding to the rat cortex and striatum was inhibited by thioperamide with IC30 values of 1.0 and 1.5 mg/kg, respectively. Clobenpropit also inhibited [125I]iodophenpropit binding, but was less potent (IC30: 18 and 19 mg/kg in the rat cortex and striatum, respectively) than thioperamide. Similar results were obtained in experiments with mouse whole brain (3.5 and 13 mg/kg for thioperamide and clobenpropit), indicating that there is no important species differences in the brain penetration of these drugs between rats and mice. These findings suggest that after peripheral injection both in rat and mouse thioperamide penetrates the blood-brain barrier more efficiently compared to clobenpropit. 相似文献
17.
The effects of injection of prostaglandin (PG) I2 into the cerebral ventricle on cardiovascular responses and their modification by intracerebroventricular (i.c.v.) pretreatment with several drugs were studied in male Wistar rats under urethane anesthesia. When injected into the ventricle, PG I2 (50 nmol/kg) caused a decrease in blood pressure and an increase in heart rate which were of short duration and were significantly inhibited by i.c.v. pretreatment with drugs, such as atropine (0.4 mumol/kg) and diphenhydramine (1 mumol/kg), having an anticholinergic effect. The similar effects induced by intravenous (i.v.) injection of PG I2 (5 nmol/kg) were not inhibited by i.v. pretreatment with these drugs. These results suggest that PG I2 play a role in regulation of cardiovascular function through central muscarinic acetylcholine receptors. 相似文献
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Recently, using molecular cloning approaches, three new neuropeptide Y (NPY)/peptide YY (PYY) receptors have been described in rodent brain, with pharmacological profiles that differ from the three previously described Y1, Y2 and Y3 NPY receptors and the Y4 pancreatic polypeptide- (PP-) preferring receptor. Two of these new receptors are spice variants and are called Y5 receptors, whilst a third receptor has been called Y6 and has been suggested to be expressed only in the mouse. In the absence of a totally selective Y5 and/or Y6 radioligands, we have examined [125I]PYY(3–36) binding, which binds Y2 and Y5/Y6 receptors, using homogenate assays and quantitative receptor autoradiography to study the distribution of the three newly discovered Y5/Y6 receptors by masking binding to Y1 receptors with high concentrations of the non-peptidergic selective Y1 antagonist, BIBP3226, and using either [Leu31,Pro34]NPY or human PP to mask binding to Y5 and Y6 receptors, leaving binding to Y2 receptors. Using this approach, [125I]PYY(3–36) labels a small population of Y1 receptors and a larger population of binding sites that are insensitive to BIBP3226, human PP and [Leu31,Pro34]NPY, presumed to be Y2 receptors. There was also [125I]PYY(3–36) binding to sites sensitive to NPY, human PP and [Leu31,Pro34]NPY, but insensitive to BIBP3226, located in the hypothalamus, amygdala, hippocampus and thalamus. As one of the recently cloned Y5 receptors is synthesized in these regions, as shown by in-situ hybridization techniques, we suggest that the small population of [125I]PYY(3–36) binding sites which are sensitive to human PP and [Leu31,Pro34]NPY, but insensitive to BIBP3226, may represent binding to Y5 receptors. We have been unable, however, to visualize a smaller population of Y6 receptors which are labelled by [125I]PYY3–36 and sensitive to [Leu31,Pro34]NPY, but not to BIBP3226 and human PP, confirming that the murine Y6 receptor does not appear to be expressed in rat brain. 相似文献
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In human cortex and hippocampus area, [3H]5-HT (5 nM) labels 5-HT1A, 5-HT1D and 5-HT1E sites. After masking 5-HT1A receptors by 0.1 μM 8-OH-DPAT, the binding displaced by 0.1 μM 5-CT presumably represented 5-HT1D sites and the remaining binding 5-HT1E sites. In frontal cortex, 5-HT1A receptors represented the main binding in layers II and VI and a lower fraction on other layers. 5-HT1D and 5-HT1E sites, were more homogeneously distributed in layers II to VI (21–34% of specific [3H]5-HT binding). 5-HT1E sites were of similar affinities (KD close to 6–8 nM) in the cortical layers II to VI. In CA1 field of hippocampus, (pyramidal layer, stratum radiatum, molecular layer), CA2 and dentate gyrus, 5-HT1A receptors represented the major fraction, 5-HT1D sites a significant fraction and 5-HT1E a minor fraction of the specific [3H]5-HT binding. In CA3–CA4 fields, 5-HT1A receptors were less densely present, 5-HT1D sites were predominant and 5-HT1E sites represented a significant fraction (27%). The highest densities of 5-HT1E sites have been measured in subiculum, where 5-HT1A, 5-HT1D, and 5-HT1E binding sites were equally represented and in entorhinal cortex where 5-HT1E sites represented the major binding in layer III. They were also present in layers II and IV (29 and 24%) and, to a lesser extent, in layers V and VI. 5-HT1A sites were predominant in layer VI, II and V and were less abundant in other layers. 5-HT1D were homogeneously present in layers II, III, IV and were present in low amounts in other layers. No 5-HT1E were detected in choroid plexus, where [3H]5-HT was dramatically reduced by mesulergine (5-HT2C receptors). No significant displacement of [3H]5-HT by mesulergine was measured in other structures. 相似文献
20.
Kurita M Nishino S Ohtomo K Rai M Shirakawa H Mashiko H Niwa S Nakahata N 《Progress in neuro-psychopharmacology & biological psychiatry》2007,31(3):600-604
Sodium valproate (VPA) has been used clinically for treatment of not only epilepsy but also mood disorder. Although VPA is effective for treatment of epilepsy via inhibition of gamma-aminobutyric acid transaminase, it remains unknown why VPA is effective for the treatment of mood disorder. The authors examined the effect of VPA at therapeutic concentrations (300 and 600 microM) on the elevation of intracellular free calcium concentration ([Ca(2+)](i)) induced by carbachol, a muscarinic receptor agonist, in 1321N1 human astrocytoma cells. Treatment of the cells with 300 and 600 microM VPA for 2 min did not change the carbachol-induced [Ca(2+)](i) elevation. Treatment with 300 and 600 microM VPA for 48 h, however, reduced the elevation. Since we have shown that Li(+) reduced carbachol-induced [Ca(2+)](i) elevation in protein kinase C (PKC)-downregulated 1321N1 cells [Kurita, M., Mashiko, H., Rai, M., Kumasaka, T., Kouno, S., Niwa, S., Nakahata, N., 2002. Lithium chloride at a therapeutic concentration reduces Ca(2+)response in protein kinase C down-regulated human astrocytoma cells, Eur. J. Pharmacol. 442, 17-22.], the activity of PKC was examined. Treatment with VPA at the same concentrations for 24 or 48 h weakly reduced protein kinase C activity in membrane and cytosol fractions from the cells. On the other hand, the treatment of the cells with 600 microM VPA for 24 or 48 h slightly increased the B(max) value, but not the K(d) value, in the binding of [(3)H]quinuclidinyl benzylate, a muscarinic receptor ligand, to the membranes, suggesting that the number or affinity of muscarinic receptor did not decrease after VPA treatment. These results indicate that VPA at therapeutic concentrations slightly decreases the PKC activity and inhibits muscarinic receptor-mediated [Ca(2+)](i) elevation probably through change in the intracellular signaling pathway. VPA-induced reduction of PKC activity and [Ca(2+)](i) elevation may play a role in the treatment of mood disorder. 相似文献