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Publications (1)5.81 Total impact

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    ABSTRACT: The alpha1A-adrenergic receptor (α1A-AR) regulates various vascular functions and participates in the pathogenesis of primary hypertension. However, highly specific and subtype-selective antagonists of α1A-AR have not been developed. Two novel antibodies against the short peptides CP-7, which is located in the second extracellular loop of α1A-AR, and CPE-8, which is located in the third extracellular loop of α1A-AR, were prepared. The two antibodies specifically bound to α1A-AR. However, neither antibody prevented [(3)H]-epinephrine or [(3)H]-prazosin from binding to the receptor. In vitro, the anti-CP-7 antibody inhibited Ca(2+)-dependent signal transduction processes including protein kinase C translocation and extracellular signal-regulated kinase (ERK1/2) phosphorylation induced by phenylephrine (PHE). The anti-CP-7 antibody decreased the beating rates of neonatal rat cardiomyocytes with or without PHE stimulation and reduced the blood pressure of spontaneously hypertensive rats that were immunized with CP-7-keyhole limpet haemocyanin. The anti-CP-7 antibody specifically inhibited the activation of α1A-AR both in vitro and in vivo. No competition binding was found between anti-CP-7 and [(3)H]-epinephrine or [(3)H]-prazosin. An antibody that specifically inhibits a receptor could be useful in research on G-protein-coupled receptors that lack specific antagonists. The antibody against the epitope CP-7 might have potential in a therapeutic application for treating primary hypertension.
    Cardiovascular research 11/2011; 93(2):280-90. · 5.81 Impact Factor