Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin
| Autor: | Melanie J. Robbins, Robert P. Davis, Guillaume Hervieu, Paul R. Murdock, Nicole C. Herrity, Catherine E. Ellis, Kim Winborn, Graham J. Riley, Jane E. Bolaky, Carol A. Jennings, Andrew D. Medhurst, John G. Darker, Kenneth W. M. Lawrie |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Arginine G protein Blotting Western Central nervous system Endogeny Peptide Biology Ligands Binding Competitive Biochemistry Cell Line Receptors G-Protein-Coupled Mice Radioligand Assay Structure-Activity Relationship Cellular and Molecular Neuroscience Adipokines Internal medicine Cyclic AMP medicine Animals Humans Fluorometry Receptor Apelin receptor chemistry.chemical_classification Apelin Receptors Receptors Dopamine D2 Reverse Transcriptase Polymerase Chain Reaction Brain Immunohistochemistry Rats Apelin Cell biology Endocrinology medicine.anatomical_structure Amino Acid Substitution Spinal Cord chemistry Organ Specificity Mutagenesis Site-Directed Intercellular Signaling Peptides and Proteins Carrier Proteins Protein Binding |
| Zdroj: | Journal of Neurochemistry. 84:1162-1172 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1046/j.1471-4159.2003.01587.x |
| Popis: | Apelin peptides have recently been identified to be the endogenous ligands for the G protein-coupled receptor APJ. However, little is known about the physiological roles of this ligand-receptor pairing. In the present study we investigated the pharmacology of several apelin analogues at the human recombinant APJ receptor using radioligand binding and functional assays. This has led to the identification of key residues in the apelin peptide required for functional potency and binding affinity through structure-activity studies. In particular, we have identified that replacement of leucine in position 5, or arginine in position 2 and 4 of the C-terminal apelin peptide, apelin-13, resulted in significant changes in pharmacology. We also investigated the detailed localization of pre-proapelin and APJ receptor mRNA in a wide range of human, rat and mouse tissues using quantitative RT-PCR, and carried out a detailed immunohistochemical study of the distribution of the APJ receptor in rat brain and spinal cord. Interestingly, the APJ receptor was not only co-localized in white matter with GFAP in the spinal cord, but was also clearly localized on neurones in the brain, suggesting that this receptor and its peptide may be involved in a wide range of biological process yet to be determined. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text