Adrenomedullin 2 and 5 activate the calcitonin receptor-like receptor (clr) – Receptor activity-modifying protein 3 (ramp3) receptor complex in Xenopus tropicalis

Maho Ogoshi, Mikoto Takahashi, Kota Aoyagi, Kazuyoshi Ukena, Sayaka Aizawa, Hideaki Takeuchi, Sumio Takahashi, Sakae Takeuchi

Research output: Contribution to journalArticlepeer-review

Abstract

The adrenomedullin (AM) family is involved in diverse biological functions, including cardiovascular regulation and body fluid homeostasis, in multiple vertebrate lineages. The AM family consists of AM1, AM2, and AM5 in tetrapods, and the receptor for mammalian AMs has been identified as the complex of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2) or RAMP3. However, the receptors for AM in amphibians have not been identified. In this study, we identified the cDNAs encoding calcrl (clr), ramp2, and ramp3 receptor components from the western clawed frog (Xenopus tropicalis). Messenger RNAs of amphibian clr and ramp2 were highly expressed in the heart, whereas that of ramp3 was highly expressed in the whole blood. In HEK293T cells expressing clr-ramp2, cAMP response element luciferase (CRE-Luc) reporter activity was activated by am1. In HEK293T cells expressing clr-ramp3, CRE-Luc reporter activity was increased by the treatment with am2 at the lowest dose, but with am5 and am1 at higher dose. Our results provided new insights into the roles of AM family peptides through CLR-RAMP receptor complexes in the tetrapods.

Original languageEnglish
Article number113752
JournalGeneral and Comparative Endocrinology
Volume306
DOIs
Publication statusPublished - 2021 May 15

Keywords

  • Adrenomedullin
  • Luciferase reporter assay
  • Receptor activity
  • cAMP production

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Endocrinology

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