Journal article
Activation of relaxin family receptor 1 from different mammalian species by relaxin peptide and small molecule agonist ML290
Z Huang, C Myhr, RAD Bathgate, B Ho, A Bueno, X Hu, J Xiao, N Southall, E Barnaeva, IU Agoulnik, JJ Marugan, M Ferrer, AI Agoulnik
Frontiers in Endocrinology | FRONTIERS MEDIA SA | Published : 2015
Abstract
Relaxin peptide (RLN), which signals through the relaxin family peptide 1 (RXFP1) GPCR receptor, has shown therapeutic effects in an acute heart failure clinical trial. We have identified a small molecule agonist of human RXFP1, ML290; however, it does not activate the mouse receptor. To find a suitable animal model for ML290 testing and to gain mechanistic insights into the interaction of various ligands with RXFP1, we have cloned rhesus macaque, pig, rabbit, and guinea pig RXFP1s and analyzed their activation by RLN and ML290. HEK293T cells expressing macaque or pig RXFP1 responded to relaxin and ML290 treatment as measured by an increase of cAMP production. Guinea pig RXFP1 responded to r..
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Grants
Awarded by National Science Foundation
Funding Acknowledgements
The authors thank Dr. O. David Sherwood, University of Illinois, for providing porcine relaxin; Prof. John D. Wade, Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia, for providing mouse relaxin peptide; Corthera, Inc. (San Mateo, CA, USA) for providing recombinant human relaxin and Sharon Layfield and Tania Ferraro for technical assistance with studies at the Florey and Shashank Pawitwar and Supurna Dhar for their help in cloning rabbit and guinea pig receptors. This research was supported by Florida Department of Health, James and Esther King Biomedical Research Program grant 3KFO1, and National Cancer Institute grant 1U01CA177711 (AA). Research at the Florey was supported by National Health and Medical Research Council of Australia project grants 628427 and 1043750 and by the Victorian Government Operational Infrastructure Support Program. RADB is a recipient of an NHMRC Research Fellowship. BH is a recipient of a MARC U*STAR program fellowship at the Florida International University.