Receptor Activity Modifying Proteins (RAMPs) Interact with the VPAC(2) Receptor and CRF(1) Receptors and modulate their function.

Summary of "Receptor Activity Modifying Proteins (RAMPs) Interact with the VPAC(2) Receptor and CRF(1) Receptors and modulate their function."

BACKGROUND AND
PURPOSE:
Although it is established the receptor activity modifying proteins (RAMPs) can interact with a number of G-protein coupled receptors (GPCRs), little is known about the consequences of these interactions. Here the interaction of RAMPs with the glucagon-like peptide 1 receptor (GLP-1 receptor), the human vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating peptide 2 receptor (VPAC(2) ) and the type 1 corticotrophin releasing factor receptor (CRF(1) ) has been examined. EXPERIMENTAL
APPROACH:
GPCRs were co-transfected with RAMPs in HEK 293S and CHO-K1 cells. Cell surface expression of RAMPs and GPCRs was examined by ELISA. Where there was evidence for interactions, agonist-stimulated cAMP production, Ca(2+) mobilisation and GTPγS binding to Gs Gi, G(12) and Gq were examined. The ability of CRF to stimulate adrenal corticotrophic hormone release in Ramp2(+/-) mice was assessed. KEY
RESULTS:
The GLP-1 receptor failed to enhance the cell surface expression of any RAMP. VPAC(2) enhanced the cell surface expression of all three RAMPs. CRF(1) enhanced the cell surface expression of RAMP2; the cell surface expression of CRF(1) was also increased. There was no effect on agonist-stimulated cAMP production. However, there was enhanced G-protein coupling in a receptor and agonist-dependent manner. The CRF(1) :RAMP2 complex resulted in enhanced elevation of intracellular calcium to CRF and urocortin 1 but not sauvagine. In Ramp2(+/-) mice, there was a loss of responsiveness to CRF. CONCLUSIONS AND
IMPLICATIONS:
The VPAC(2) and CRF(1) receptors interact with RAMPs. This modulates G-protein coupling in an agonist-specific manner. For CRF(1) , coupling to RAMP2 may be of physiological significance.

Affiliation

School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria, 3052, Australia.

Journal Details

This article was published in the following journal.

Name: British journal of pharmacology
ISSN: 1476-5381
Pages:

Links

• PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22946657
• DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.02202.x