Single-Cell Characterization of Endothelin System Gene Expression in the Cerebellum In Situ

Schmidt‐Ott, Kai M.; Tuschick, Sebastian; Kirchhoff, Frank; Verkhratsky, A; Liefeldt, Lutz; Kettenmann, Helmut; Paul, Martin

doi:10.1097/00005344-199800001-00102

Cited by 18 publications

(10 citation statements)

References 6 publications

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“…Bergmann glia and astrocytes in the granular layer might synthesize ETs for autostimulatory regulation within 2 weeks. In contrast, mRNA of the ET-converting enzymes ECE-1 and ECE-2, are expressed in a substantial number of Purkinje cells in rats at 3-4 weeks (Schmidt-Ott et al 1998), and ET-1 immunoreactivity was observed in the human Purkinje cells (Giaid et al 1991). This may indicate ET-mediated local interaction in Purkinje cells and Bergmann glia under certain conditions.…”

Section: Discussionmentioning

confidence: 89%

Localization of endothelin-A and -B receptors during the postnatal development of rat cerebellum

Furuya

Hiroe

Ogiso

et al. 2001

Cell and Tissue Research

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Intense expression of mRNA of endothelin-B receptor (ETBR) has been detected in the Bergmann glia of cerebellum by in situ hybridization, but the intracellular localization has not been reported because of the absence of a useful antibody for immunohistochemical investigations. We made polyclonal antibodies against the carboxyl terminus of human ETBR (420-442) and ETAR (403-427), and performed light- and electron-microscopic immunohistochemistry of the wild-type and ETBR-deficient (sl/sl) rat cerebella. Localization of ETBR during postnatal development was examined by double-staining immunofluorescence using antibodies against ETBR and S-100 beta. In the wild-type rats, ETBR immunoreactivity appeared from postnatal day 5 (P5) and was distributed diffusely in the processes and cell bodies of S-100 beta-positive glial cells. By P14, ETBR immunoreactivity was concentrated in the Golgi apparatus of Bergmann glial cell soma and the plasma membrane of its processes. The ETBR-positive astrocytes in the granular layer decreased in number during P7-14 and had disappeared by week 3. At 3 weeks, ETBR immunoreactivity was restricted to the Golgi apparatus of Bergmann glia. In the sl/sl rats, ETBR immunoreactivity was not observed at all. In contrast to ETBR, ETAR immunoreactivity appeared transiently in the cytoplasm of all astrocytes (Bergmann glia and astrocytes in the granular layer) in the 9- to 14-day-old wild rats and 7- to 14-day-old sl/sl rats, and disappeared within 3 weeks in both. Granule cells did not express immunoreactivity for ETBR and ETAR from the neonatal stage to adulthood. Changes in the intracellular localization of ETBR and transient expression of ETAR may be correlated with the changes of glial functions and proliferation during postnatal development of rat cerebellum.

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Section: Discussionmentioning

confidence: 89%

Localization of endothelin-A and -B receptors during the postnatal development of rat cerebellum

Furuya

Hiroe

Ogiso

et al. 2001

Cell and Tissue Research

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“…The animal was inserted in a mouse restrainer B60" Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) served as internal control. The following primers were used at concentrations of 0.25 mM (0.2 mM for preproET-1) : GAPDH (sense) 5h-GCCATCAA-CGACCCCTTCATTG-3h, GAPDH (anti-sense) 5h-TGCCAGTGAGCTTCCCGTTC-3h [5], ET A (sense) 5h-GGCGCAATCGCTGACAATGCTGAG-3h, ET A (anti-sense) 5h-CCACGTAGATAAGGTCTCCAAG-GG-3h, ET B (sense) 5h-CGTGTTCGTGCTAGGCAT-CATCGG-3h, ET B (anti-sense) 5h-CGACTCCAAGA-AGCAACAGCTCGA-3h [6], preproET-1 (sense) 5h-TGTGTCTACTTCTGCCACCT-3h, preproET-1 (antisense) 5h-CACCAGCTGCTGATAGATAC-3h [7], AT-1a (sense) 5h-TCACCTGCATCATCATCTGG-3h AT-1a (anti-sense) 5h-AGCTGGTAAGAATGATTA-GG-3h, AT-1b (anti-sense) 5h-AGCTGGTGAGAATA-ATAACG-3h (the sense primer for AT-1b was the same as that for AT-1a), AT-2 (sense) 5h-CTGACCCT-GAACATGTTTGCA-3h, AT-2 (anti-sense) 5h-GGT-GTCCATTTCTCTAAGAG-3h [8], angiotensinogen (sense) 5h-CATCCGCCTGACTCTGC-3h, angiotensinogen (anti-sense) 5h-GGCCTTGTCTCCATGGC-3h [9]. The cycle profiles were of denaturation for 2 min at 94 mC, annealing at each suitable temperature and extension for 5 min at 72 mC.…”

Section: Blood Pressure (Bp) Measurementmentioning

confidence: 99%

Role of endothelin receptors in the hypertensive state of kinin B2 knockout mice subjected to a high-salt diet

et al. 2002

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Mice with disruption of the kinin B(2) receptor (B(2)KO mice) are sensitive to salt-rich diets, which causes hypertension. The aim of the study was to assess the role of endothelin-1 (ET-1) and angiotensin-II in hypertensive B(2)KO mice on a salt-rich diet. We also wanted to verify if there is an upregulation of the mRNA expression of the precursors or receptors for these hormones. Two groups of B(2)KO mice (20-25 g) were investigated. The first group received an 8% NaCl diet with 1% NaCl in drinking water (HS) and the second was fed with normal food with tap water (NS). The antagonists tested were the ET(A) receptor antagonist BQ-123 (1 and 5 mg/kg), the ET(B) receptor antagonist BQ-788 (0.25 and 1 mg/kg), the angiotensin receptor type 1 antagonist losartan (10 mg/kg) and the angiotensin-converting enzyme inhibitor captopril (3 mg/kg). These were injected intraperitoneally 30 min prior to blood pressure measurement by the tail-cuff method. We also studied the level of expression of preproET-1, ET-1 receptors, angiotensinogen and angiotensin receptors by RNA extraction from the heart and kidneys of these mice followed by reverse transcriptase (RT)-PCR. B(2)KO mice (HS) were hypertensive after 8 weeks compared with B(2)KO mice on normal diet (HS, 93.4+/-1.5 mmHg, n=7; NS, 61.4+/-2.7 mmHg, n=7). In the HS group, the mean arterial blood pressure was significantly reduced by BQ-123 (5 mg/kg) to 61.9+/-1.8 mmHg (n=7), by BQ-788 (1 mg/kg) to 58.8+/-2.6 mmHg (n=6), by losartan (10 mg/kg) to 73.2+/-1.7 mmHg (n=8) and by captopril (3 mg/kg) to 86.0+/-2.3 mmHg (n=8). The expression studied by RT-PCR did not show any difference (either in precursors or receptors expression) between hypertensive and normal mice. The four antagonists used seemed to reverse the hypertension. These results suggest that ET-1 and angiotensin-II are probably involved in the mechanism that leads to hypertension since the effect of these hormones is probably not compensated by kinins in B(2)KO mice. Further studies are necessary to understand the implication of the cross-talk between these hormones in the hypertensive state.

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“…Two ECE family members, ECE-1 and ECE-2, both showing preference for big ET-1 over either big ET-2 or big ET-3 in vitro, have been identified. These two protease are expressed in several cell types, such as endothelial cells [119], glia [148], neurons [121] and glial cell lines [7], but have different requirements for their catalytic activity. ECE-1 has a sharp activity peak at neutral pH and processes big ETs both inside the cell and on the cell surface, whilst ECE-2 displays a sharp activity peak at pH 5.5 suggesting that ECE-2 is likely the protease responsible for the conversion of endogenously synthesized big ETs to mature ETs inside the cell in acidified compartments such as the trans-Golgi network.…”

Section: Introduction Biosynthesis Of Endothelinsmentioning

confidence: 99%

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Schinelli¹

2006

CMC

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The endothelin system, consisting of three peptides, two peptidases and two G-protein coupled receptors, is widely expressed in the brain cell types and brain-derived tumor cell lines. The stimulation of endothelin receptors elicits a variety of short- and long-term changes at cellular level but the effects of the pharmacological modulation of the endothelin system in brain physiology and pathophysiology are, at the present time, poorly understood. Altered expression of endothelins (ETs) in reactive astrocytes has been observed in many pathological conditions of the human brain, such as infarcts, lacunae, traumatic conditions, Alzheimer's disease and inflammatory diseases of the brain. In addition, recent studies have shown that endothelin antagonists might inhibit growth and induce cell death in human melanoma cells in vitro and in vivo, and have emphasized a possible role of endothelin peptides as autocrine or paracrine factor in the proliferation and dissemination of tumor cell lines. Given the fact that brain cell and a variety of brain tumor cell lines express functional endothelin receptors, further studies are warranted to demonstrate a possible therapeutic role of endothelin agonists and antagonist in the pharmacological treatment of brain-related diseases and brain tumors.

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Single-Cell Characterization of Endothelin System Gene Expression in the Cerebellum In Situ

Cited by 18 publications

References 6 publications

Localization of endothelin-A and -B receptors during the postnatal development of rat cerebellum

Localization of endothelin-A and -B receptors during the postnatal development of rat cerebellum

Role of endothelin receptors in the hypertensive state of kinin B2 knockout mice subjected to a high-salt diet

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

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