Single type-2 astrocytes show multiple independent sites of Ca2+ signaling in response to histamine.

Inagaki, Naoyuki; Fukui, Hirokazu; Ito, Seiji; Yamatodani, Atsushi; Wada, Hiroshi

doi:10.1073/pnas.88.10.4215

Cited by 60 publications

(36 citation statements)

References 39 publications

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“…Several studies have shown the existence of histamine H 1 receptors on cultured astrocytes. [39][40][41] More recent studies have shown that astrocytes have histamine H 1 receptors in situ. 42 The most prominent neuropathologic feature of HE is the alteration of astrocyte morphology and function.…”

Section: Discussionmentioning

confidence: 99%

Increased density of brain histamine H1 receptors in rats with portacaval anastomosis and in cirrhotic patients with chronic hepatic encephalopathy

Lozeva¹

2001

Hepatology

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The binding properties and the regional densities of histamine H 1 receptors were studied in brain of rats with portacaval anastomosis (PCA) and in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy (HE). Receptor binding studies and quantitative receptor autoradiography were performed, employing [ 3 H]mepyramine. Histamine H 1 receptors in rat brain displayed a higher density and a lower affinity compared with control human frontal cortex. Specific [ 3 H]mepyramine binding was heterogeneously distributed throughout the brain in both species. In human brain, binding was highest in the parietal and temporal cortices and lowest in caudate-putamen. In rat brain, binding was highest in the suprachiasmatic nucleus, dentate gyrus of the hippocampus, ventromedial hypothalamus, and nucleus accumbens. Hepatic encephalopathy (HE) is a potential long-term complication of chronic liver disease. Despite extensive research and a succession of different hypotheses, the exact mechanisms underlying the development of the clinical symptoms of HE are not well understood. 1,2 Consequently, progress in the treatment of HE in cirrhotic patients has been limited. Among the least exploited consequences of HE are the marked changes in the brain histaminergic system, which have been previously documented both in patients with HE 3 and in rats with portacaval anastomosis (PCA), a well-established animal model of the disease. [4][5][6][7][8] There is substantial evidence that histamine acts as a neurotransmitter in mammalian brain. 9 Histaminergic neurons are located exclusively in the tuberomammillary nucleus of the posterior hypothalamus and send their varicose fibers to almost every region of the brain. 10 This widespread distribution of histaminergic neurons suggests that the brain histaminergic system is involved in the regulation of a wide range of neurobiologic functions. Histaminergic signaling is mediated by 3 types of receptors, histamine H 1 , H 2 , and H 3 receptors, distinguished by their pharmacologic properties, specific anatomic location, and by the intracellular responses they mediate. 11,12 Interest has focused on the histamine H 1 receptors, because histamine, through the activation of the postsynaptic histamine H 1 receptors, is involved in the regulation of the neuroendocrine system, 13,14 locomotor activity, 15-17 circadian rhythmicity, 18,19 and the sleep-wake cycle, 20 as well as in various behaviors, including feeding and drinking (for a review, see Schwartz, 9 Yamatodani et al., 21 and Sakata 22 ).We have previously shown that altered histaminergic neurotransmission is an important part of the neurophysiologic background responsible for the behavioral changes after PCA surgery in the rat, leading us to propose that it may contribute to the pathogenesis of HE in human subjects. [6][7][8] Relating the functions controlled by histamine to the clinical presentation of HE, it appears a priori that histamine could participate in the pathogenesis of the sleep disturbances, decreased spontaneous vo...

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Section: Discussionmentioning

confidence: 99%

Increased density of brain histamine H1 receptors in rats with portacaval anastomosis and in cirrhotic patients with chronic hepatic encephalopathy

Lozeva¹

2001

Hepatology

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“…Previous studies have demonstrated the existence of CaMKII in astrocytes (26,28), and CaMKII activated by Ca 2ϩ was shown to phosphorylate vimentin in these cells (19,26). Furthermore, they display local and global Ca 2ϩ signaling in response to neurotransmitters (8,29 (Fig. 1, G-J).…”

Section: Spatial Signaling From Ca 2ϩ Via Camkii To Vimentinmentioning

confidence: 99%

“…[Ca 2ϩ ] i Measurements-The [Ca 2ϩ ] i of cultured astrocytes was measured as described elsewhere (8,24). Briefly, the cells were incubated…”

Section: Methodsmentioning

confidence: 99%

“…Cell Preparation and Drug Application-Primary cultured astrocytes (type 1 astrocytes) were prepared from the cerebral cortices of newborn rats as described previously (19 ] i of cultured astrocytes was measured as described elsewhere (8,24). Briefly, the cells were incubated * This research was supported in part by Grants-in-Aid for Scientific Research and Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan, and special coordination funds from the Science and Technology Agency of the Government of Japan.…”

Section: Methodsmentioning

confidence: 99%

“…Ionomycin or prostaglandin F 2␣ (PGF 2␣ ) dissolved in HEPESbuffered Krebs-Ringer solution (containing the following (in mM): NaCl, 115; KCl, 5.4; CaCl 2 , 2; MgCl 2 , 0.8; glucose, 13.8; Hepes, 20 (pH 7.4)) were bath applied, or locally applied using a micropipette (Sterile Femtotips, Eppendorf) equipped with Transjector 5246 (Eppendorf) by pressure (30 hPa). The flow speed of the locally applied solution was 0.05-0.1 l/h.[Ca 2ϩ ] i Measurements-The [Ca 2ϩ ] i of cultured astrocytes was measured as described elsewhere (8,24). Briefly, the cells were incubated…”

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confidence: 99%

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Spatial Patterns of Ca2+ Signals Define Intracellular Distribution of a Signaling by Ca2+/Calmodulin-dependent Protein Kinase II

Inagaki¹,

Goto²,

Ogawara³

et al. 1997

Journal of Biological Chemistry

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Cell signaling is the fundamental strategy by which cells respond to extracellular stimuli. Intracellular distribution of cell signaling is considered to be an important factor affecting the manner in which cells respond to extracellular stimuli with spatial specificity (1, 2). Although little is known of the spatial aspect of cell signaling, that of Ca 2ϩ signaling visualized by Ca 2ϩ microscopy is presently the best characterized example. Numbers of reports have shown that intracellular Ca 2ϩ signals occur locally and globally (3-6). The intracellular distribution of Ca 2ϩ signaling in various types of cells was defined by the amplitude and direction of extracellular stimuli (7-10). Therefore, it has been speculated that spatial patterns of Ca 2ϩ signals might be transmitted, as a form of cellular information, by a downstream molecule that induces Ca 2ϩ -dependent cellular responses (1-2, 6 -10).To address this issue, we visualized site-specific phosphorylation of vimentin by CaMKII 1 and Ca 2ϩ signaling in the same astrocytes. CaMKII is located downstream of Ca 2ϩ signaling and is thought to regulate various cellular responses (11,12). Vimentin is an intermediate filament protein distributed widely in the cytoplasm (13,14) and is phosphorylated by several protein kinases, including CaMKII, in vivo (15, 16). Therefore, vimentin can serve as a substrate for the examination of the cytoplasmic distribution of protein kinase activities (17, 18). Here we report that vimentin phosphorylation by CaMKII was induced locally and globally by Ca 2ϩ signaling. The intracellular area of the phosphorylation was precisely defined by that of Ca 2ϩ signaling. EXPERIMENTAL PROCEDURESPreparation of Antibodies, Peptides, and Proteins-Production of monoclonal antibodies YT33, TM50, 4A4, and MO82 was reported elsewhere (19 -21). Vimentin peptides PV6 (Cys-Ser-Thr-Arg-Ser-Val-phosphoSer 6 -Ser-Ser-Ser-Tyr-Arg), V6 (Cys-Ser-Thr-Arg-Ser-Val-Ser-SerSer-Ser-Tyr-Arg), PV38 (Cys-Ser-Thr-Arg-Thr-Tyr-phosphoSer 38 -LeuGly-Ser-Ala-Leu), and V38 (Cys-Ser-Thr-Arg-Thr-Tyr-Ser-Leu-Gly-SerAla-Leu) were synthesized as described previously (21). A monoclonal antibody against PV6 (MO6) and a polyclonal antibody against PV38 (GK38) were produced following the methods described previously (21, 22) Then the specificity of MO6 and GK38 was checked by enzymelinked immunosorbent assay (21). MO6 bound to PV6 but not to the unphosphorylated peptide V6, while GK38 reacted with PV38 but not with the unphosphorylated form V38. Production of recombinant vimentin and vimentin phosphorylated by CaMKII was described previously (19). The affinity-purified antibody specific for both 50-and 60-kDa subunits of CaMKII (23) was provided by Drs. K. Fukunaga and E. Miyamoto (Kumamoto University).Cell Preparation and Drug Application-Primary cultured astrocytes (type 1 astrocytes) were prepared from the cerebral cortices of newborn rats as described previously (19). Two days before the experiments, astrocytes were subcultured on collagen (type 1, Sigma)-coated glass coversl...

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Receptor-mediated calcium signalling in glial cells from mouse corpus callosum slices

et al. 1996

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Single type-2 astrocytes show multiple independent sites of Ca2+ signaling in response to histamine.

Cited by 60 publications

References 39 publications

Increased density of brain histamine H1 receptors in rats with portacaval anastomosis and in cirrhotic patients with chronic hepatic encephalopathy

Increased density of brain histamine H1 receptors in rats with portacaval anastomosis and in cirrhotic patients with chronic hepatic encephalopathy

Spatial Patterns of Ca2+ Signals Define Intracellular Distribution of a Signaling by Ca2+/Calmodulin-dependent Protein Kinase II

Receptor-mediated calcium signalling in glial cells from mouse corpus callosum slices

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