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Book ; Thesis: Isoenzyme von Adenylyl-Cyclasen in Neuroblastomazellinien

Leemhuis, Jost

1998

Author's details	vorgelegt von Jost Leemhuis
Language	German
Size	92 S. : Ill., graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Düsseldorf, Univ., Diss., 1998
HBZ-ID	HT011106101
Database	Catalogue ZB MED Medicine, Health

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Article: Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study.

Weber, Martin S / Buttmann, Mathias / Meuth, Sven G / Dirks, Petra / Muros-Le Rouzic, Erwan / Eggebrecht, Julius C / Hieke-Schulz, Stefanie / Leemhuis, Jost / Ziemssen, Tjalf

Frontiers in neurology

2022 Volume 13, Page(s) 863105

Abstract: Background: Real-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of ... ...

Abstract	Background: Real-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of patients newly treated with ocrelizumab. Methods: CONFIDENCE (ML39632, EUPAS22951) is an ongoing multicenter, non-interventional post authorization safety study assessing patients with RMS or PPMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. For this analysis, patients newly treated with ocrelizumab were analyzed in subgroups by MS phenotype and age over a mean ~1 year of exposure totaling 2,329 patient years [PY]). Results: At data cutoff (14 October 2020), 1,702 patients with RMS and 398 patients with PPMS were treated with ≥1 dose of ocrelizumab. At baseline, the mean ages (SD) of patients with RMS and PPMS were 41.59 (11.24) and 50.95 (9.88) years and the mean EDSS (Expanded Disability Status Scale) was 3.18 (1.87) and 4.41 (1.59), respectively. The most common adverse events (AEs) and serious AEs across both phenotypes were infections and infestations, with infection SAE rates of 2.8 events/100 PY and 1.5 events/100 PY in patients with RMS and PPMS, respectively. Across all phenotypes, ocrelizumab persistence was 92% at 24 months; median time between doses was ~6 months. Conclusions: The ocrelizumab safety profile observed in the CONFIDENCE real-world MS population was consistent to the one observed in pivotal clinical trials. High treatment persistence and adherence were observed. Trial registration: ML39632, EUPAS22951.
Language	English
Publishing date	2022-05-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.863105
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Article ; Online: Design of a non-interventional post-marketing study to assess the long-term safety and effectiveness of ocrelizumab in German real world multiple sclerosis cohorts - the CONFIDENCE study protocol.

Dirks, Petra / Zingler, Vera / Leemhuis, Jost / Berthold, Heike / Hieke-Schulz, Stefanie / Wormser, David / Ziemssen, Tjalf

BMC neurology

2020 Volume 20, Issue 1, Page(s) 95

Abstract: Background: Multiple sclerosis (MS) is a chronic disease that requires lifelong treatment. A highly effective drug not only for relapsing but also for progressive forms of MS with a favorable safety profile is needed to further improve overall patient ... ...

Abstract	Background: Multiple sclerosis (MS) is a chronic disease that requires lifelong treatment. A highly effective drug not only for relapsing but also for progressive forms of MS with a favorable safety profile is needed to further improve overall patient outcomes. Ocrelizumab, a recombinant humanized monoclonal antibody that selectively targets CD20-expressing B-cells, is the first drug indicated for the treatment of adult patients with relapsing forms of MS (RMS) and primary progressive MS (PPMS). Its safety and effectiveness profile has yet to be studied in a large, real-world setting. CONFIDENCE aims to further characterize the safety profile of ocrelizumab in routine clinical practice. In addition, real-world effectiveness data will be collected to complement the efficacy data documented in the pivotal clinical trials. Methods: CONFIDENCE is a non-interventional, prospective, multicenter, long-term study collecting primary data from 3000 RMS and PPMS patients newly treated with ocrelizumab and 1500 patients newly treated with other selected MS disease-modifying therapies (DMTs). Treatment must be in accordance with the local label and follow routine practice. Data will be collected at approximately 250 neurological centers and practices across Germany. The recruitment period of 30 months started in April 2018. The observation period per patient is planned 7.5 to 10 years, depending on the date of inclusion, regardless of whether patients discontinue treatment. Visits follow routine practice and will be documented approximately every 6 months. The primary endpoint is the incidence and type of uncommon adverse events and death. Statistical analyses will be mainly descriptive and exploratory. Discussion: CONFIDENCE is a large, non-interventional, post-authorization safety study that assesses long-term safety and effectiveness of ocrelizumab and other DMTs in a real-world setting. Data collected in CONFIDENCE will also be integrated into studies that have been developed to fulfil international regulatory requirements.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Germany ; Humans ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Product Surveillance, Postmarketing ; Prospective Studies ; Research Design
Chemical Substances	Antibodies, Monoclonal, Humanized ; ocrelizumab (A10SJL62JY)
Language	English
Publishing date	2020-03-14
Publishing country	England
Document type	Journal Article ; Multicenter Study
ISSN	1471-2377
ISSN (online)	1471-2377
DOI	10.1186/s12883-020-01667-7
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Article ; Online: Reelin modulates cytoskeletal organization by regulating Rho GTPases.

Leemhuis, Jost / Bock, Hans H

Communicative & integrative biology

2011 Volume 4, Issue 3, Page(s) 254–257

Abstract: The correct positioning of postmitotic neurons in the developing neocortex and other laminated brain structures requires the activation of a Reelin-lipoprotein receptor-Dab1 signaling cascade. The large glycoprotein Reelin is secreted by Cajal-Retzius ... ...

Abstract	The correct positioning of postmitotic neurons in the developing neocortex and other laminated brain structures requires the activation of a Reelin-lipoprotein receptor-Dab1 signaling cascade. The large glycoprotein Reelin is secreted by Cajal-Retzius pioneer neurons and bound by the apolipoprotein E receptor family members Apoer2 and Vldl receptor on responsive neurons and radial glia. This leads to the tyrosine phosphorylation of the cytoplasmic protein Disabled-1 (Dab1) by non-receptor tyrosine kinases of the Src family. Various signaling pathways downstream of Dab1 connect Reelin to the actin and microtubule cytoskeleton. Despite this knowledge, a comprehensive view linking the different cell-biological and biochemical actions of Reelin to its diverse physiological roles not only during neurodevelopment but also in the maintenance and functioning of the adult brain is still lacking. In this review, we discuss our finding that Reelin activates Rho GTPases in neurons in the light of other recent studies, which demonstrate a role of Reelin in Golgi organization, and suggest additional roles of Cdc42 activation by Reelin in radial glial cells of the developing cortex.
Language	English
Publishing date	2011-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2451097-X
ISSN	1942-0889 ; 1942-0889
ISSN (online)	1942-0889
ISSN	1942-0889
DOI	10.4161/cib.4.3.14890
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Article ; Online: Ocrelizumab Treatment in Patients with Primary Progressive Multiple Sclerosis: Short-term Safety Results from a Compassionate Use Programme in Germany.

Rauer, Sebastian / Hoshi, Muna-Miriam / Pul, Refik / Wahl, Mathias / Schwab, Matthias / Haas, Judith / Ellrichmann, Gisa / Krumbholz, Markus / Tackenberg, Björn / Saum, Kai-Uwe / Buck, Fabian / Leemhuis, Jost / Kretschmann, Anita / Aktas, Orhan

Clinical neurology and neurosurgery

2020 Volume 197, Page(s) 106142

Abstract: Objectives: In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a ... ...

Abstract	Objectives: In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a phase 3 randomised controlled trial. Eleven months prior to the European regulatory approval, a compassionate use programme (CUP) made ocrelizumab available to 489 patients with PPMS in Germany, thereby for the first time providing a therapeutic option to patients with PPMS who could not participate in ocrelizumab studies. Here, we report real-world patient characteristics and short-term safety data of patients with PPMS treated with ocrelizumab in this CUP. Patients and methods: This CUP was initiated in February 2017 - shortly before US Food and Drug administration approval in March 2017 - and ended in January 2018, following ocrelizumab approval in the EU. Adult patients (age ≥18 years) with PPMS who had a positive benefit/risk ratio according to the treating physician were eligible for inclusion at German treatment centres. The main exclusion criteria were current/recent treatment with other immune therapies and unresolved/chronic/active infections. Patients received methylprednisolone and an antihistamine before treatment with intravenous ocrelizumab in 6-month cycles. The first ocrelizumab dose was a 300 mg infusion followed by a second 300 mg infusion 2 weeks later; subsequent doses were delivered as a single 600 mg infusion. Adverse events were reported immediately. Results: Of 580 requests received from 104 centres, 525 patients met the eligibility criteria. Thirty-five patients did not participate due to withdrawal by the treating physician, and one due to death prior to treatment. A total of 489 patients received at least one 600 mg dose of ocrelizumab (administered as two 300 mg infusions) and 51 received a second dose. Due to termination of the CUP upon marketing authorisation, the maximum follow-up period was 12 months. Median patient age was 52 years (range: 24-73), and 49% were female. Previous immunomodulatory or immunosuppressive therapies had been received by 41% of patients, with the most commonly used being glucocorticoids, mitoxantrone, interferon-β and glatiramer acetate. Patients with a previous malignancy, serious disease or infection (42 patients, 9%) had recovered from this prior to the CUP. Nine serious adverse events and 70 non-serious adverse events were reported in 40 patients. Adverse event categories were generally consistent with the known safety profile of ocrelizumab; one patient had carry-over progressive multifocal leukoencephalopathy (PML) due to previous natalizumab treatment. Conclusion: This CUP provides first real-world observations of ocrelizumab for the treatment of PPMS in a large patient cohort in Germany, supporting that ocrelizumab is generally well-tolerated in clinical practice. Physicians should be vigilant for early symptoms of PML, as to date, 9 PML cases that were all confounded have been reported in patients treated with ocrelizumab worldwide, with 8 carry-over cases from a prior DMT.
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal, Humanized/therapeutic use ; Compassionate Use Trials ; Female ; Germany ; Humans ; Immunologic Factors/therapeutic use ; Immunotherapy/methods ; Male ; Middle Aged ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Treatment Outcome ; Young Adult
Chemical Substances	Antibodies, Monoclonal, Humanized ; Immunologic Factors ; ocrelizumab (A10SJL62JY)
Language	English
Publishing date	2020-08-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	193107-6
ISSN	1872-6968 ; 0303-8467
ISSN (online)	1872-6968
ISSN	0303-8467
DOI	10.1016/j.clineuro.2020.106142
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Book ; Thesis: Isoenzyme von Adenylyl-Cyclasen in Neuroblastomazellinien

Leemhuis, Jost

1998

Author's details	vorgelegt von Jost Leemhuis
Language	German
Size	92 S, Ill., graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Düsseldorf, 1998
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Rho kinase inhibitors Y27632 and H1152 augment neurite extension in the presence of cultured Schwann cells.

Fuentes, Erick O / Leemhuis, Jost / Stark, G Björn / Lang, Eva M

Journal of brachial plexus and peripheral nerve injury

2008 Volume 3, Page(s) 19

Abstract: Background: RhoA and Rho kinase inhibitors overcome the inhibition of axonal regeneration posed by central nervous system (CNS) substrates.: Methods: To investigate if inhibition of the Rho pathway augments the neurite extension that naturally occurs ...

Abstract	Background: RhoA and Rho kinase inhibitors overcome the inhibition of axonal regeneration posed by central nervous system (CNS) substrates. Methods: To investigate if inhibition of the Rho pathway augments the neurite extension that naturally occurs in the peripheral nervous system (PNS) following nerve damage, dorsal root ganglion neurons and Schwann cell co-cultures were incubated with culture medium, C3 fusion toxin, and the Rho kinase (ROCK) inhibitors Y27632 and H1152. The longest neurite per neuron were measured and compared. Incubation with Y27632 and H1152 resulted in significantly longer neurites than controls when the neurons were in contact with Schwann cells. When separated by a porous P.E.T. membrane, only the group incubated with H1152 developed significantly longer neurites. This work demonstrates that Rho kinase inhibition augments neurite elongation in the presence of contact with a PNS-like substrate.
Language	English
Publishing date	2008-09-25
Publishing country	United States
Document type	Journal Article
ISSN	1749-7221
ISSN (online)	1749-7221
DOI	10.1186/1749-7221-3-19
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Article ; Online: Role of GluN2A and GluN2B subunits in the formation of filopodia and secondary dendrites in cultured hippocampal neurons.

Henle, Frank / Dehmel, Martina / Leemhuis, Jost / Fischer, Catharina / Meyer, Dieter K

Naunyn-Schmiedeberg's archives of pharmacology

2011 Volume 385, Issue 2, Page(s) 171–180

Abstract: GluN receptors are heteromers of obligatory GluN1 subunits and GluN2(A-D) subunits. In the present study, we addressed the question whether GluN2A and GluN2B subunits play distinct roles in the formation of filopodia and dendrites during the early ... ...

Abstract	GluN receptors are heteromers of obligatory GluN1 subunits and GluN2(A-D) subunits. In the present study, we addressed the question whether GluN2A and GluN2B subunits play distinct roles in the formation of filopodia and dendrites during the early development of hippocampal neurons. In hippocampal neurons brought into culture at embryonic day 17, we studied 2-3 days later the effects of N-methyl-D-aspartic acid (NMDA) on the numbers of filopodia, growth cones, and primary as well as secondary dendrites. Antagonists specific for GluN2A and GluN2B subunits were applied together with NMDA. NMDA only induced the formation of filopodia and secondary dendrites. Whereas filopodia were generated within 15 min by NMDA alone, secondary dendrites were only induced by the joint application of NMDA and the Rho kinase inhibitor Y-27632 for 24 h. The GluN2B antagonists ifenprodil and Ro 25-6981 prevented the NMDA-induced formation of filopodia, whereas the GluN2A antagonists NVP-AAM007 and EAA-090 prevented the formation of secondary dendrites. We conclude that both GluN2 subunits have differential roles in dendritic arborization.
MeSH term(s)	Animals ; Azabicyclo Compounds/pharmacology ; Cells, Cultured ; Dendrites/drug effects ; Dendrites/physiology ; Excitatory Amino Acid Agonists/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; HeLa Cells ; Hippocampus/cytology ; Humans ; N-Methylaspartate/pharmacology ; Neurons/drug effects ; Neurons/physiology ; Organophosphonates/pharmacology ; Phenols/pharmacology ; Piperidines/pharmacology ; Protein Subunits/antagonists & inhibitors ; Protein Subunits/physiology ; Pseudopodia/drug effects ; Pseudopodia/physiology ; Quinoxalines/pharmacology ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate/physiology
Chemical Substances	5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione ; Azabicyclo Compounds ; Excitatory Amino Acid Agonists ; Excitatory Amino Acid Antagonists ; NR2B NMDA receptor ; Organophosphonates ; Phenols ; Piperidines ; Protein Subunits ; Quinoxalines ; Receptors, N-Methyl-D-Aspartate ; Ro 25-6981 ; N-Methylaspartate (6384-92-5) ; EAA-090 (FX5AUU7Z8T) ; ifenprodil (R8OE3P6O5S) ; N-methyl D-aspartate receptor subtype 2A (VH92ICR8HX)
Language	English
Publishing date	2011-10-28
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-011-0701-3
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Article ; Online: Reelin induces EphB activation.

Bouché, Elisabeth / Romero-Ortega, Mario I / Henkemeyer, Mark / Catchpole, Timothy / Leemhuis, Jost / Frotscher, Michael / May, Petra / Herz, Joachim / Bock, Hans H

Cell research

2013 Volume 23, Issue 4, Page(s) 473–490

Abstract: The integration of newborn neurons into functional neuronal networks requires migration of cells to their final position in the developing brain, the growth and arborization of neuronal processes and the formation of synaptic contacts with other neurons. ...

Abstract	The integration of newborn neurons into functional neuronal networks requires migration of cells to their final position in the developing brain, the growth and arborization of neuronal processes and the formation of synaptic contacts with other neurons. A central player among the signals that coordinate this complex sequence of differentiation events is the secreted glycoprotein Reelin, which also modulates synaptic plasticity, learning and memory formation in the adult brain. Binding of Reelin to ApoER2 and VLDL receptor, two members of the LDL receptor family, initiates a signaling cascade involving tyrosine phosphorylation of the intracellular cytoplasmic adaptor protein Disabled-1, which targets the neuronal cytoskeleton and ultimately controls the positioning of neurons throughout the developing brain. However, it is possible that Reelin signals interact with other receptor-mediated signaling cascades to regulate different aspects of brain development and plasticity. EphB tyrosine kinases regulate cell adhesion and repulsion-dependent processes via bidirectional signaling through ephrin B transmembrane proteins. Here, we demonstrate that Reelin binds to the extracellular domains of EphB transmembrane proteins, inducing receptor clustering and activation of EphB forward signaling in neurons, independently of the 'classical' Reelin receptors, ApoER2 and VLDLR. Accordingly, mice lacking EphB1 and EphB2 display a positioning defect of CA3 hippocampal pyramidal neurons, similar to that in Reelin-deficient mice, and this cell migration defect depends on the kinase activity of EphB proteins. Together, our data provide biochemical and functional evidence for signal integration between Reelin and EphB forward signaling.
MeSH term(s)	Animals ; Binding Sites ; COS Cells ; Cell Adhesion Molecules, Neuronal/genetics ; Cell Adhesion Molecules, Neuronal/metabolism ; Cerebral Cortex/cytology ; Cerebral Cortex/embryology ; Cerebral Cortex/metabolism ; Chlorocebus aethiops ; Embryo, Mammalian ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/metabolism ; Gene Expression Regulation, Developmental ; LDL-Receptor Related Proteins/genetics ; LDL-Receptor Related Proteins/metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuronal Plasticity ; Neurons/cytology ; Neurons/metabolism ; Phosphorylation ; Protein Binding ; Protein Structure, Tertiary ; Receptor, EphB1/genetics ; Receptor, EphB1/metabolism ; Receptor, EphB2/genetics ; Receptor, EphB2/metabolism ; Receptors, LDL/genetics ; Receptors, LDL/metabolism ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Signal Transduction/genetics
Chemical Substances	Cell Adhesion Molecules, Neuronal ; Dab1 protein, mouse ; Extracellular Matrix Proteins ; LDL-Receptor Related Proteins ; Nerve Tissue Proteins ; Receptors, LDL ; VLDL receptor ; low density lipoprotein receptor-related protein 8 ; Receptor, EphB1 (EC 2.7.10.1) ; Receptor, EphB2 (EC 2.7.10.1) ; Serine Endopeptidases (EC 3.4.21.-) ; reelin protein (EC 3.4.21.-)
Language	English
Publishing date	2013-01-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/cr.2013.7
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Article ; Online: Sympathetic alpha(2)-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload.

Gilsbach, Ralf / Schneider, Johanna / Lother, Achim / Schickinger, Stefanie / Leemhuis, Jost / Hein, Lutz

Cardiovascular research

2010 Volume 86, Issue 3, Page(s) 432–442

Abstract: Aims: alpha(2)-Adrenoceptors modulate cardiovascular function by vasoconstriction or dilatation, by central inhibition of sympathetic activity, or by feedback inhibition of norepinephrine release from sympathetic neurons. Despite detailed knowledge ... ...

Abstract	Aims: alpha(2)-Adrenoceptors modulate cardiovascular function by vasoconstriction or dilatation, by central inhibition of sympathetic activity, or by feedback inhibition of norepinephrine release from sympathetic neurons. Despite detailed knowledge about subtype-specific functions of alpha(2)-receptors, the relative contributions of sympathetic vs. non-sympathetic receptors involved in these cardiovascular effects have not been identified. The aim of this study was to define the physiological and pharmacological role of alpha(2A)-adrenoceptors in adrenergic vs. non-adrenergic cells at baseline and during sympathetic stress. Methods and results: Transgenic mice expressing alpha(2A)-adrenoceptors under control of the dopamine beta-hydroxylase (Dbh) promoter were generated and crossed with mice carrying a constitutive deletion in the alpha(2A)- and alpha(2C)-adrenoceptor genes. alpha(2AC)-deficient mice showed increased norepinephrine plasma levels, cardiac hypertrophy, and fibrosis at baseline. Expression of the Dbh-alpha(2A) transgene in sympathetic neurons prevented these effects. In contrast, Dbh-alpha(2A) receptors mediated only a minor part of the bradycardic and hypotensive effects of the alpha(2)-agonist medetomidine. After chronic pressure overload as induced by transverse aortic constriction in mice, the Dbh-alpha(2A) transgene did not reduce norepinephrine spillover, cardiac dysfunction, hypertrophy, or fibrosis. In isolated wild-type atria, alpha(2)-agonist-induced inhibition of [3H]norepinephrine release was significantly desensitized after pressure overload. In primary sympathetic neurons from Dbh-alpha(2A) transgenic mice, norepinephrine and medetomidine induced endocytosis of alpha(2A)-adrenoceptors into neurite processes. Conclusion: alpha(2A)-Adrenoceptors expressed in adrenergic cells are essential feedback inhibitors of sympathetic norepinephrine release to prevent cardiac hypertrophy and fibrosis at baseline. However, these receptors are desensitized by chronic pressure overload which in turn may contribute to the pathogenesis of this condition.
MeSH term(s)	Adrenergic alpha-Agonists/pharmacology ; Animals ; Blood Pressure/drug effects ; Cardiomegaly/etiology ; Cardiomegaly/genetics ; Cardiomegaly/metabolism ; Cardiomegaly/pathology ; Cardiomegaly/prevention & control ; Cells, Cultured ; Disease Models, Animal ; Dopamine beta-Hydroxylase/genetics ; Dose-Response Relationship, Drug ; Endocytosis ; Feedback, Physiological ; Fibrosis ; Gene Expression Profiling ; Heart/innervation ; Heart Rate/drug effects ; Humans ; Hypertension/complications ; Hypertension/genetics ; Hypertension/metabolism ; Hypertension/pathology ; Medetomidine/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Myocardium/metabolism ; Myocardium/pathology ; Neurites/drug effects ; Neurites/metabolism ; Norepinephrine/blood ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Receptors, Adrenergic, alpha-2/deficiency ; Receptors, Adrenergic, alpha-2/genetics ; Receptors, Adrenergic, alpha-2/metabolism ; Sympathetic Fibers, Postganglionic/drug effects ; Sympathetic Fibers, Postganglionic/metabolism ; Sympathetic Nervous System/metabolism ; Sympathetic Nervous System/physiopathology
Chemical Substances	ADRA2A protein, human ; ADRA2C protein, human ; Adra2a protein, mouse ; Adra2c protein, mouse ; Adrenergic alpha-Agonists ; RNA, Messenger ; Receptors, Adrenergic, alpha-2 ; Dopamine beta-Hydroxylase (EC 1.14.17.1) ; Medetomidine (MR15E85MQM) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2010-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvq014
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