Cloning and functional characterization of the amphibian mesotocin receptor, a member of the oxytocin/vasopressin receptor superfamily

Aida Akhundova, Elena Getmanova, Valentin Gorbulev, Eric Carnazzi, Patrick Eggena, Falk Fahrenholz

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Mesotocin is the oxytocin-like hormone found in most terrestrial vertebrates from lungfishes to marsupials, which includes all non-mammalian tetrapods (amphibians, reptiles, and birds). It has the largest distribution in vertebrates after vasotocin found in all non-mammalian vertebrates and isotocin identified in bony fishes. In this study, we report the cloning and functional characterization of the cDNA for the mesotocin receptor (MTR) from the urinary bladder of the toad Bufo marinus. The cloned cDNA encodes a polypeptide of 389 amino acids that shows the greatest similarity to the teleost fish isotocin receptor and to mammalian oxytocin receptors with mutations in extracellular loops which are involved in ligand binding. When expressed in COSM6 cells, MTR exhibits the following relative order of ligand affinity: mesotocin > vasotocin = oxytocin > vasopressin > hydrin 1, isotocin, hydrin 2. Injection of MTR cRNA into Xenopus laevis oocytes induces membrane chloride currents in response to mesotocin, which indicates the coupling of the mesotocin receptor to the inositol phosphate/calcium pathway. This response is inhibited by an oxytocin antagonist, but not by a vasopressin antagonist specific for V, vasopressin receptors. MTR mRNA is not only found in toad urinary bladder, but also in kidney, muscle, and brain tissue of the toad as revealed by Northern blot analysis and reverse-transcriptase PCR. The results suggest a variety of functions for mesotocin and its receptor including, in particular, an involvement in the regulation of water and salt transport.

Original languageEnglish
Pages (from-to)759-767
Number of pages9
JournalEuropean Journal of Biochemistry
Volume237
Issue number3
DOIs
StatePublished - 1996

Keywords

  • Hormone-binding site
  • Mesotocin receptor
  • Molecular evolution
  • Terrestrial amphibians
  • Water transport

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