By Kazuo Kitamura, Kenji Kangawa, Tanenao Eto (auth.), Toshio Nishikimi MD, PhD (eds.)
Adrenomedullin was once came upon in 1993 in an extract of human pheochromocytoma whereas tracking cAMP degrees in rat platelets. Adrenomedullin has attracted massive curiosity between cardiologists because of its impression at the cardiovascular procedure which incorporates a lessen in blood strain in vivo; an influence on vascular delicate muscle cells; raises cAMP degrees; in some way reduces blood strain and has a task within the pathogenesis of arteriosclerosis.
Adrenomedullin in heart problems is an updated assessment of the main suitable elements of adrenomedullin. It features a huge diversity of fields together with biochemistry, molecular biology, body structure, pharmacology, pathophysiology of heart problems and scientific purposes of adrenomedullin to cardiovascular disease.
Toshio Nishikimi, MD, PhD, is an affiliate Professor within the division of high blood pressure and Cardiorenal medication, Dokkyo college college of medication, Tochigi, Japan.
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Additional info for Adrenomedullin in Cardiovascular Disease
Angiotensin II type 1 receptor Sympathetic nerve activity receptor Hypertension pi receptor" AM receptor CRE? AP-2 DAG PKi AM Gene Expression (INR) HIF-1 Oncoprotein Figure 4. Shear ' stress NF-IL6 \ Inflammation j myc Carcinogenesis SSRE? I Hypoxia Ischemia IL-1 TNF-a IPS Putative regulatory mechanism of adrenomeduflin (AM) gene expression. PLC, 50 phospholipase C; DAG, diacylglycerol; PKC, protein kinase C; IL-1, interleukin-1; TNF-a, tumor necrosis factor a; LPS, lipopolysaccharide; AP-2, activator protein 2; CRE, cAMP responsive element; SSRE, shear stress responsive element; NF-EL6, nuclear factor for interleukin-6 expression; HIF-1, hypoxia-inducible factor-1; INR, initiator element 4.
1993), cAMP was initially considered to be a major intracellular signaling molecule for AM. , 1994a). , 1994a). , 2002), where CRLR belongs to family B of GPCR as characterized by functional coupling to Gs (Gether, 2000). , 1998). , 1996). , 1996). , 1997). On the other hand, cAMP/PKA pathway is widely recognized as a negative regulator of cell growth. , 1996). , 1997), whose effect was mediated via cAMP/PKA pathway. , 2003). Collectively, it is suggested that bi-functional role of AM for cell growth control; in quiescent cells AM exerts its mitogenic action via PTK/ERK pathway (as discussed in the following section), whereas AM exerts its anti-mitogenic action via cAMP/PKA pathway in asynchronously growing cells (Fig.
Nussdorfer GG, Rossi GP, and Mazzocchi G. (1997) Role of adrenomedullin and related peptides in the regulation of the hypothalamo-pituitary-adrenal axis. Peptides 18:1079-1089. Oehler MK, Norbury C, Hague S, Rees MC, and Bicknell R. (2001) Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth. Qncogene 20:2937-2945. Okumura H, Nagaya N, Itoh T, Okano I, Hino J, Mori K, Tsukamoto Y, IshibashiUeda H, Miwa S, Tambara K, Toyokuni S, Yunati C, and Kangawa K.