Decreased gene expression of adrenomedullin receptor in mouse lungs during sepsis.
Plasma concentrations of adrenomedullin (AM) are markedly increased during sepsis, but the role of AM has not been clarified. Coexpression of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP) 2 or 3 have been reported to form the adrenomedullin (AM) specific receptor. We examined the expression of CRLR and RAMP1, 2, and 3 in several tissues from mice in a sepsis model induced by lipopolysaccharide (LPS). High expression of CRLR and RAMP2 mRNA was observed in lungs of normal mice, but it was markedly decreased in endotoxemic mice. It is suggested that the abundant binding sites of AM in lungs are formed by CRLR and RAMP2 in healthy subjects and that their reduction should contribute to the increase of plasma AM concentrations during sepsis. In contrast, LPS treatment markedly increased RAMP3 gene expression in lungs, spleen, and thymus. It is revealed that the distributions of receptor or binding sites of AM are changed in sepsis, and it is suggested that AM plays distinct roles in the clinical course of this syndrome.
Ono
Y
Y
Department of Anesthesiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
Okano
I
I
Kojima
M
M
Okada
K
K
Kangawa
K
K
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D058286:Calcitonin Receptor-Like Protein; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D012313:RNA / Q000378:metabolism; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000096:biosynthesis; D018000:Receptors, Peptide / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D018805:Sepsis / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; C545579:Calcrl protein, mouse; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C545502:RAMP1 protein, human; C545503:RAMP2 protein, human; C545504:RAMP3 protein, human; C545505:Ramp1 protein, mouse; C545506:Ramp2 protein, mouse; C545507:Ramp3 protein, mouse; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018000:Receptors, Peptide; D012313:RNA