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Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain
Abstract
Apelin, a peptide recently isolated from bovine stomach tissue extracts, has been identified as the endogenous ligand of the human orphan APJ receptor. We established a stable Chinese hamster ovary (CHO) cell line expressing a gene encoding the rat apelin receptor fused to the enhanced green fluorescent protein, to investigate internalization and the pharmacological profile of the apelin receptor. Stimulation of this receptor by the apelin fragments K17F (Lys1‐Phe‐Arg‐Arg‐Gln‐Arg‐Pro‐Arg‐Leu‐Ser‐His‐Lys‐Gly‐Pro‐Met‐Pro‐Phe17) and pE13F (pGlu5‐Arg‐Pro‐Arg‐Leu‐Ser‐His‐Lys‐Gly‐Pro‐Met‐Pro‐Phe17) resulted in a dose‐dependent inhibition of forskolin‐induced cAMP production and promoted its internalization. In contrast, the apelin fragments R10F (Arg8‐Leu‐Ser‐His‐Lys‐Gly‐Pro‐Met‐Pro‐Phe17) and G5F (Gly13‐Pro‐Met‐Pro‐Phe17) were inactive. The physiological role of apelin and its receptor was then investigated by showing for the first time in rodent brain: (i) detection of apelin neurons in the supraoptic and paraventricular nuclei by immunohistochemistry with a specific polyclonal anti‐apelin K17F antibody; (ii) detection of apelin receptor mRNA in supraoptic vasopressinergic neurons by in situ hybridization and immunohistochemistry; and (iii) a decrease in vasopressin release following intracerebroventricular injection of K17F, or pE13F, but not R10F. Thus, apelin locally synthesized in the supraoptic nucleus could exert a direct inhibitory action on vasopressinergic neuron activity via the apelin receptors synthesized in these cells. Furthermore, central injection of pE13F significantly decreased water intake in dehydrated normotensive rats but did not affect blood pressure. Together, these results suggest that neuronal apelin plays an important role in the central control of body fluid homeostasis.
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Cited by
Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity
Boucher, J., Masri, B., Daviaud, D., Gesta, S., Guigné, C., Mazzucotelli, A., Castan-Laurell, I., Tack, I., Knibiehler, B., Carpéné, C., et al. (2005) · Endocrinology · doi:10.1210/en.2004-1427 · Cited by 910
Taheri, S., Murphy, K., Cohen, M., Sujkovic, E., Kennedy, A., Dhillo, W., Dakin, C., Sajedi, A., Ghatei, M., & Bloom, S. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2002.6575 · Cited by 314
Cosacak, M. I., Bhattarai, P., Reinhardt, S., Petzold, A., Dahl, A., Zhang, Y., & Kizil, C. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.090 · Cited by 116
Zhu, J., Gao, W., Shan, X., Wang, C., Wang, H., Shao, Z., Dou, S., Jiang, Y., Wang, C., & Cheng, B. (2020) · Brain Research · doi:10.1016/j.brainres.2019.146493 · Cited by 65
Sancandi, M., Uysal-Onganer, P., Kraev, I., Mercer, A., & Lange, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082743 · Cited by 41
Metadata
- Authors
- Reaux, A., De Mota, N., Skultetyova, I., Lenkei, Z., El Messari, S., Gallatz, K., Corvol, P., Palkovits, M., & Llorens‐Cortès, C.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2001-05-15
- Volume
- 77
- Issue
- 4
- Pages
- 1085-1096
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1511152517
- Cited by
- 374
- References
- 0
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- closed
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- Reaux, A., De Mota, N., Skultetyova, I., Lenkei, Z., El Messari, S., Gallatz, K., Corvol, P., Palkovits, M., & Llorens‐Cortès, C. (2001). Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. Journal of Neurochemistry. https://doi.org/10.1046/j.1471-4159.2001.00320.x
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