Disease relevance of ADM

• Adrenomedullin (AM) is a potent hypotensive peptide originally isolated from pheochromocytoma tissue [1].
• These findings elucidate the coordinate expression of two local vascular hormones, ET and Am, under oxidative stress, which may protect against vascular diseases [2].
• Adrenomedullin (AM) and adrenomedullin binding protein (AM-BP) in the bovine mammary gland and milk: Effects of stage of lactation and experimental intramammary E. coli infection [3].
• On the other hand, hypoxia induced, and tumor necrosis factor-alpha (10 ng/ml) decreased, the expression levels of endothelin-1 and adrenomedullin mRNAs, indicating that the bovine brain microvascular endothelial cells were able to respond to hypoxia and tumor necrosis factor-alpha [4].

High impact information on ADM

• The biological action of adrenomedullin, a novel hypotensive peptide, on bovine aortic endothelial cells, was examined [5].
• Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2+ mobilization, in bovine aortic endothelial cells [5].
• Thus, the results suggest that adrenomedullin elicits the hypotensive effect through at least two mechanisms, a direct action on vascular smooth muscle cells to increase intracellular cAMP and an action on endothelial cells to stimulate nitric oxide release, with both leading to vascular relaxation [5].
• The Ca2+ response to adrenomedullin was biphasic with an initial transient increase due to the release from thapsigargin-sensitive intracellular Ca2+ storage and a prolonged increase by influx through the ion channel on the plasma membrane [5].
• PURPOSE: To assess and characterize the vasorelaxing effect of adrenomedullin (AM) on isolated bovine retinal arteries (BRAs) [6].

Biological context of ADM

• Both cAMP accumulation and Ca2+ increased responses to adrenomedullin were mediated by cholera toxin-sensitive G protein, but the two signal transduction pathways were independent [5].
• Adrenomedullin (AM) has been characterized as an endogenous tissue survival factor and modulator of many inflammatory processes [3].
• Adrenomedullin acts as a local mediator of vascular homeostasis through interactions which lead to reduced endothelin-1 synthesis and secretion [7].

Anatomical context of ADM

• Adrenomedullin (11-26): a novel endogenous hypertensive peptide isolated from bovine adrenal medulla [1].
• These studies aimed to determine the effect of ADM on ET-1 synthesis in bovine aortic endothelial cells (BAEC) and to identify the possible mechanisms involved [8].
• Underlying disease stress augments plasma and tissue adrenomedullin (AM) responses to endotoxin: colocalized increases in AM and inducible nitric oxide synthase within pancreatic islets [9].
• We studied whether the cAMP-dependent pathway is involved in the regulation of synthesis and release of adrenomedullin and proadrenomedullin N-terminal 20 peptide in cultured bovine adrenal chromaffin cells [10].
• Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the iris sphincter muscle cells [11].

Associations of ADM with chemical compounds

• In this cell model, ADM increased cyclic AMP production by BAEC with threshold concentrations of 100 pM and an EC(50) of 1 nM [8].
• In contrast, H(2)O(2) increased Am secretion (and its mRNA expression) accompanied by the augmentation of cAMP production [2].
• Relaxant effect of adrenomedullin on bovine isolated iris sphincter muscle under resting conditions [11].
• The adrenomedullin-stimulated 45Ca2+ efflux was not inhibited by incubation with Ca2+-free medium, but was inhibited by incubation with Na+-free medium [12].
• The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin [11].

Regulatory relationships of ADM

• Inhibitory effect of adrenomedullin on basal and tumour necrosis factor alpha-stimulated endothelin-1 synthesis in bovine aortic endothelial cells is independent of cyclic AMP [8].

Other interactions of ADM

• Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells [2].
• Expression of endothelin-1 and adrenomedullin was not altered by leptin or resistin in bovine brain microvascular endothelial cells [4].

References