Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Decreased gene expression of adrenomedullin receptor in mouse lungs during sepsis. 1077 2

The typical cardiovascular response to polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Although the factors and/or mediators responsible for producing the transition from the hyperdynamic to the hypodynamic stage are not fully understood, recent studies have suggested that adrenomedullin (AM), a potent vasodilatory peptide, appears to play an important role in initiating the hyperdynamic response following the onset of sepsis. In addition, the reduced vascular responsiveness to AM may result in the transition from the early, hyperdynamic phase to the late, hypodynamic phase of sepsis. It is possible that changes in newly reported AM receptors calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein-2 or -3 (RAMP2, RAMP3) as well as AM binding protein-1 (AMBP-1) may also play distinct roles in the biphasic cardiovascular response observed during sepsis. Although it remains unknown whether AM gene delivery or a chronic increase in vascular AM production in transgenic animals attenuates the development of hypodynamic sepsis and septic shock, it has been shown that modulation of AM vascular responsiveness with pharmacologic agents reduces sepsis-induced mortality. It has been recently demonstrated that AMBP-1 enhances AM's physiologic effects and plasma levels of AMBP-1 decrease following infections. We therefore propose that downregulation of AMBP-1 and the reduced AM receptor responsiveness are crucial factors responsible for the transition from the hyperdynamic phase to the hypodynamic phase of sepsis.
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PMID:Andrenomedullin and cardiovascular responses in sepsis. 1175 70

Adrenomedullin (AM) is a highly conserved peptide that can act as a potent vasodilator, anti-microbial factor and anti-inflammatory factor. Several studies have implicated diverse roles for AM in regulating the inflammatory and hemodynamic responses to septic shock. Moreover, during sepsis the receptors that mediate AM signaling [calcitonin receptor-like receptor (calcrl) and receptor activity modifying proteins (RAMP) 2 and 3] undergo dynamic and robust changes in their expression. Although numerous studies have used animal models to study the role of administered or increased AM in septic animals, genetic studies to determine the consequences of reduced AM during septic shock have not yet been performed. Here, we used a murine model of lipopolysaccharide (LPS)-induced septic shock to assess the inflammatory response in mice heterozygous for the AM gene. Following LPS challenge, AM(+/-) mice had higher expression of TNF-alpha and IL-1beta than LPS-treated wild-type (WT) controls. Consequently, serum TNF-alpha was also significantly elevated in LPS-treated AM(+/-) mice compared to WT LPS-treated mice. We also observed higher serum levels of liver enzymes, suggesting more advanced end-organ damage in mice with genetically reduced AM. Finally, we found that RAMP2 and calcrl expression levels were markedly reduced in LPS-treated mice, whereas RAMP3 expression was significantly elevated. Importantly, these changes in receptor gene expression were conserved in AM(+/-) mice, demonstrating that AM peptide itself does not impact directly on the expression of the genes encoding its receptors. We, therefore, conclude that during septic shock the dynamic modulation of AM and its receptors primarily functions to dampen the inflammatory response.
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PMID:Mice heterozygous for adrenomedullin exhibit a more extreme inflammatory response to endotoxin-induced septic shock. 1788 65