Skip to main content

Research Repository

Advanced Search

Monoclonal anti-?1-adrenergic receptor antibodies activate G protein signaling in the absence of ?-arrestin recruitment

Hutchings, Catherine J.; Cseke, Gabriella; Osborne, Greg; Woolard, Jeanette; Zhukov, Andrei; Koglin, Markus; Jazayeri, Ali; Pandya-Pathak, Jahnavi; Langmead, Christopher J.; Hill, Stephen J.; Weir, Malcolm; Marshall, Fiona H.


Catherine J. Hutchings

Gabriella Cseke

Greg Osborne

Professor of Cardiovascular Physiology and Pharmacology

Andrei Zhukov

Markus Koglin

Ali Jazayeri

Jahnavi Pandya-Pathak

Christopher J. Langmead

Professor of Molecular Pharmacology

Malcolm Weir

Fiona H. Marshall


Thermostabilized G protein-coupled receptors used as antigens for in vivo immunization have resulted in the generation of functional agonistic anti-?1-adrenergic (?1AR) receptor monoclonal antibodies (mAbs). The focus of this study was to examine the pharmacology of these antibodies to evaluate their mechanistic activity at ?1AR. Immunization with the ?1AR stabilized receptor yielded five stable hybridoma clones, four of which expressed functional IgG, as determined in cell-based assays used to evaluate cAMP stimulation. The antibodies bind diverse epitopes associated with low nanomolar agonist activity at ?1AR, and they appeared to show some degree of biased signaling as they were inactive in an assay measuring signaling through ?-arrestin. In vitro characterization also verified different antibody-receptor interactions reflecting the different epitopes on the extracellular surface of ?1AR to which the mAbs bind. The anti-?1AR mAbs only demonstrated agonist activity when in dimeric antibody format, but not as the monomeric Fab format, suggesting that agonist activation may be mediated through promoting receptor dimerization. Finally, we have also shown that at least one of these antibodies exhibits in vivo functional activity at a therapeutically-relevant dose producing an increase in heart rate consistent with ?1AR agonism.


Hutchings, C. J., Cseke, G., Osborne, G., Woolard, J., Zhukov, A., Koglin, M., …Marshall, F. H. (2014). Monoclonal anti-β1-adrenergic receptor antibodies activate G protein signaling in the absence of β-arrestin recruitment. mAbs, 6(1), 246-261.

Journal Article Type Article
Acceptance Date Nov 15, 2013
Online Publication Date Nov 19, 2013
Publication Date 2014-01
Deposit Date Jul 21, 2016
Publicly Available Date Jul 21, 2016
Journal mAbs
Print ISSN 1942-0862
Electronic ISSN 1942-0870
Publisher Taylor & Francis Open
Peer Reviewed Peer Reviewed
Volume 6
Issue 1
Pages 246-261
Keywords stabilized receptor, Beta 1 adrenergic receptor, GPCR, extracellular domain, extracellular loop, functional antibody, isoprenaline, propranolol
Public URL
Publisher URL


Monoclonal anti 1 adrenergic receptor antibodies activate G protein signaling in the absence of arrestin recruitment.pdf (3 Mb)

Copyright Statement
Copyright information regarding this work can be found at the following address:

You might also like

Downloadable Citations