Receptor activity modifying proteins (RAMPs) interact with the VPAC2 receptor and CRF1 receptors and modulate their function
| Autor: | Wootten, D, Lindmark, H, Kadmiel, M, Willcockson, H, Caron, KM, Barwell, J, Drmota, T, Poyner, DR |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Mice
Knockout Enzyme-Linked Immunosorbent Assay CHO Cells Real-Time Polymerase Chain Reaction Receptor Activity-Modifying Protein 2 Transfection Research Papers Receptors Corticotropin-Releasing Hormone Receptor Activity-Modifying Proteins Mice Cricetulus HEK293 Cells Adrenocorticotropic Hormone Guanosine 5'-O-(3-Thiotriphosphate) Cricetinae Cyclic AMP Animals Humans Receptors Vasoactive Intestinal Peptide Type II Calcium Protein Binding |
| Popis: | Although it is established that the receptor activity modifying proteins (RAMPs) can interact with a number of 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 AC-activating peptide 2 receptor (VPAC(2)) and the type 1 corticotrophin releasing factor receptor (CRF(1)) has been examined.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+) mobilization and GTPγS binding to G(s), G(i), G(12) and G(q) were examined. The ability of CRF to stimulate adrenal corticotrophic hormone release in Ramp2(+/-) mice was assessed.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.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. |
| Databáze: | OpenAIRE |
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