Submitted on October 2, 2007
Accepted on February 28, 2008
Potent cardiovascular actions of homologous adrenomedullins in eels
Shigenori Nobata1*, Maho Ogoshi2, and Yoshio Takei3
1 Div. of Physiology, Dep. of Marine Bioscience, Ocean Research Institute, University of Tokyo, Tokyo, Japan
2 Nakano, Tokyo, Japan; Div. of Physiology, Dep. of Marine Bioscience, Ocean Research Institute, University of Tokyo, Tokyo, Japan
3 Div. of Physiology, Dep. of Marine Bioscience, Ocean Research Institute, University of Tokyo, Nakano, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: nobata{at}ori.u-tokyo.ac.jp.
Adrenomedullin (AM), known as a multifunctional hormone in mammals, forms a unique family of five paralogous peptides in teleost fish. To examine their cardiovascular effects using homologous AMs in eels, we isolated cDNAs encoding four eel AMs, and named AM1 (ortholog of mammalian AM), AM2, AM3 (paralog of AM2 generated only in teleost lineage) and AM5 according to the known teleost AM sequences. Unlike pufferfish, not only AM1 but AM2/3 and AM5 were expressed ubiquitously in various eel tissues. Synthetic mature AM1, AM2 and AM5 exhibited vasodepressor effects after intra-arterial injections, and the effects were more potent at dorsal aorta (PDA) than ventral aorta (PVA). This indicates that AMs preferentially act on peripheral resistance vessels rather than on branchial arterioles. The potency was in the order of AM2=AM5>>AM1 in both FW and SW eels, which is different from the result of mammals where AM1 is as potent as, or more potent than AM2 when injected peripherally. The minimum effective dose of AM2 and AM5 in eels was 1/10 that of AM1 in mammals. The hypotension reached 50% at 1.0 nmol/kg of AM2 and AM5, which is much greater than ANP (20%), another potent vasodepressor hormone. Even with such hypotension, AMs did not change heart rate in eels. Additionally, AM1 increased PVA and PDA immediately after an initial hypotension at 5.0 nmol/kg, but not with AM2 and AM5. These data strongly suggest that specific receptors for AM2 and AM5 exist in eels, which differ from the AM1 receptors identified in mammals.
