Disease relevance of ADM2

• By activating specific receptors (likely AM2) and the PI3K/Akt/GSK3beta signaling pathway, AM could play a significant role in long-lasting heat hypersensitivity and inflammatory heat hyperalgesia [1].
• Xanthomonas campestris pv. glycines strain AM2 (XcgAM2), the aetiological agent of bacterial pustule disease of soybean, as well as some other strains of Xanthomonas including X. campestris pv. malvacearum NCIM 2310 and X. campestris NCIM 2961, exhibited post-exponential rapid cell death (RCD) in Luria-Bertani (LB) medium [2].
• In general, in cell free extracts (CFE) of the strains, the majority of proteolytic activities was highest for Lactococcus lactis HP, intermediate for L. lactis AM2 and lowest for L. lactis 303 [3].

High impact information on ADM2

• The strand breaks produced by AM2 in the dark and by mitoxantrone (with or without illumination) were protein concealed [4].
• Following a 1-h exposure to AM2, a dose of drug required to give 50% loss of cell viability (53 microM) was obtained in the dark, which was reduced to approximately 2.4 microM following illumination for 2 min (lambda greater than 475 nm), a dose of light that was completely nontoxic to the cells in the absence of drug [4].
• 1,4-Diamino-substituted anthraquinone antitumor agents (mitoxantrone and ametantrone) and structurally related 1,5- and 1,8-diamino-substituted compounds (AM1 and AM2) were tested for their ability to photosensitize human leukemic cells in culture [4].
• In vivo studies demonstrated that intermedin treatment led to blood pressure reduction in both normal and spontaneously hypertensive rats via interactions with the CRLR/RAMP receptor complexes [5].
• Furthermore, in vivo treatment in mice with intermedin led to suppression of gastric emptying activity and food intake [5].

Biological context of ADM2

• Similarity of exon-intron structure and synteny of neighboring genes showed that mammalian AM2 is an ortholog of pufferfish AM2 and a paralog of mammalian AM [6].
• Hence the mechanism of ADM2-induced vasorelaxation is nitric oxide and receptor mediated and cGMP and cAMP dependent and occurs through activation of calcium-activated potassium channels [7].
• Adrenomedullin 2 antagonist infusion to rats during midgestation causes fetoplacental growth restriction through apoptosis [8].
• The present article provides an overview of the calcitonin/intermedin family peptides found in teleost and mammalian genomes, and describes their putative functions [9].
• Two different siRNAs (AM2 and AM4) significantly reduced AML1-MTG8 expression from a transfected reporter plasmid at both the mRNA and protein levels [10].

Anatomical context of ADM2

• Analysis of intermedin expression indicated that intermedin is expressed primarily in the pituitary and gastrointestinal tract [5].
• These results show that at least two peptides, AM and AM2, comprise an adrenomedullin family in mammals, and that AM2 may play pivotal roles in cardiovascular and body fluid regulation [6].
• Inhibition of soluble guanylate cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM) or endothelial nitric oxide synthase with N-nitro-L-arginine methyl ester (100 microM) reduced the relaxation of mesenteric artery induced by ADM2 [7].
• Furthermore, incubation of endothelium intact arterial tissue from pregnant rats with ADM217-47, an ADM2 antagonist, shifted the dose-dependent relaxation curve to the right in wire myography [7].
• The mRNA of ADM2 is expressed in several tissues, including uterus and ovary [8].

Associations of ADM2 with chemical compounds

• Three adriamycin-resistant sublines (HCT-15/ADM1, HCT-15/ADM2 and HCT-15/ADM2-2) were established by stepwise exposure in growth medium that was supplemented with 25-200 ng/ml adriamycin-resulting in a 2.2- to 7.8-fold increase in IC(50) values by using the XTT assay [11].
• Blockade of calcium-activated potassium channels with tetraethylammonium chloride (1 mM) inhibited the ADM2-induced relaxation, whereas blockade of ATP-sensitive potassium channels with glybenclamide (10 microM) did not affect the relaxation response [7].
• Inhibition of adenylate cyclase with SQ22536 (10 microM) or protein kinase A with the Rp diastereomer of cyclic adenosine 3',5'-phosphorothioate (10 microM) also reduced the maximal relaxation responses induced by ADM2 [7].
• For synthesis of the AM2 analogue, novel routes via addition of nitromethane followed by conversion of the nitro function to either amino or carboxyl groups were developed [12].
• Revertants of mutant strain AM2 exhibited normal glucose and diauxie growth [13].

Other interactions of ADM2

• Adrenomedullin 2 (ADM2) is a recently discovered member of the calcitonin/calcitonin gene-related peptide family with an exon-intron structure similar to that of ADM [8].
• In order to understand the mechanism underlying multidrug resistance in bladder cancer, we established three doxorubicin-resistant cell lines, T24/ADM-1, T24/ADM-2 and KK47/ADM, and one vincristine-resistant cell line, T24/VCR, from human bladder cancer T24 and KK47 cells respectively [14].
• Recently, based on the analysis of multiple vertebrate genomes, we identified a novel calcitonin/CGRP family peptide named intermedin [9].

Analytical, diagnostic and therapeutic context of ADM2

• Intravenous injection of synthetic mature AM2 decreased arterial pressure more potently than AM, and induced antidiuresis and antinatriuresis in mice [6].
• Immunocytochemistry showed AM2/IMD-immunoreactive cell bodies in the paraventricular and supraoptic nuclei of human hypothalamus [15].
• Reverse-transcriptase polymerase chain reaction confirmed expression of AM2/IMD mRNA in the brain, pituitary, heart and kidney [15].

References