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Agonistic antibody to the alpha(1)-adrenergic receptor mobilizes intracellular calcium and induces phosphorylation of a cardiac 15-kDa protein

Item Type:Article
Title:Agonistic antibody to the alpha(1)-adrenergic receptor mobilizes intracellular calcium and induces phosphorylation of a cardiac 15-kDa protein
Creators Name:Karczewski, P. and Haase, H. and Hempel, P. and Bimmler, M.
Abstract:Hypertension is a major cause for hypertrophic remodelling of the myocardium. Agonistic autoantibodies to extracellular loops of the alpha(1)-adrenergic receptor (alpha(1)-AR) have been identified in patients with arterial hypertension. However, intracellular reactions elicited by these agonistic antibodies remain elusive. An anti-peptide antibody (anti-alpha(1)) was generated against the second extracellular loop of the alpha(1)-AR that bound to its peptide epitope with high affinity (K (D) ~50 nM). We studied anti-alpha(1) effects on intracellular calcium (Ca(i)), a key factor in cellular remodelling, and receptor-mediated cardiac protein phosphorylation. Anti-alpha(1) induced pronounced but transient increases in Ca(i) in CHO cells expressing the human alpha(1)-AR (CHO-alpha(1)) and in neonatal cardiomyocytes. Preincubation experiments failed to demonstrate a tonic effect of anti-alpha(1) on Ca(i). However, preincubation with the antibody attenuated the effect of the alpha(1)-AR antagonist prazosin. In neonatal cardiomyocytes anti-alpha(1) induced a robust phosphorylation of a 15-kDa protein that is involved in alpha(1)-AR signalling. Our data support the notion that elevation of Ca(i) is a general feature of agonistic antibodies' action and constitute an important pathogenic component of hypertension-associated autoantibodies. Furthermore, we suggest that agonistic antibodies to the alpha(1)-AR contribute to hypertrophic remodelling of cardiac myocytes, and that the cardiac 15-kDa protein is a relevant downstream target of their action.
Keywords:Agonistic Autoantibody, alpha(1)-Adrenergic Receptor, Intracellular Calcium, Protein Phosphorylation, Cardiomyocytes, CHO Cells, Animals, Rats
Source:Molecular and Cellular Biochemistry
ISSN:0300-8177
Publisher:Springer (Germany)
Volume:333
Number:1-2
Page Range:233-242
Date:January 2010
Official Publication:https://doi.org/10.1007/s11010-009-0224-0
PubMed:View item in PubMed

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