1. Adrenomedullin Peptide Structure and Related Topics

 The amino acid sequence of adrenomedullin is shown in Figure 1A. The adrenomedullin (AM) gene, which is present in humans, generates a prepro 185 amino acid peptide, followed by a pro aa164 peptide and a final 52 amino acid sequence of AM which has a widespread list of biological properties (see below). Panel A lists the final 52 amino acid sequence of AM. It includes a disulfide bond from residue 16 to 21, thus creating a 6 amino acid loop. The AM carboxy terminus has an amide group. In addition, a second biologically active, proadrenomedullin N-terminal 20 amino acid peptide, PAMP, is produced. The amino acid sequence and properties of AM display a moderate similarity to the calcitonin gene related peptide (CGRP) superfamily. The biological properties supported by the hormone adrenomedullin are separately dependent upon one of two separate AM1 and AM2 receptors. Both of the receptors belong to the seven transmembrane G protein-coupled family which produces the second messenger cAMP. However, there are reports describing other second messengers, including nitric oxide, NO, changes in intracellular Ca2+, the involvement of prostaglandins and MAP kinase. The T1/2 of AM is ~20 minutes, which is reflective of the presence of a lively production of AM as well as a relatively vigorous breakdown mechanism.

Fig1. Biochemical and biological properties for the peptide hormone adrenomedullin. (A) Adrenomedullin peptide structure. The adrenomedullin (AM) gene, which is present in humans, generates a prepro 185 amino acid peptide, followed by a pro aa164 peptide and a final 52 amino acid sequence of AM which has a widespread list of biological properties (see the following). Panel A lists the final 52 amino acid sequence of AM. It includes a disulfide bond from residue 16 to 21, thus creating a 6 amino acid loop. The AM carboxy terminus has an amide group. In addition, a second biologically active, proadrenomedullin N-terminal 20 amino acid peptide, PAMP, is produced. (B) Physiological functions of adrenomedullin. The normal circulatory concentration of AM in humans is in the range of 2–8 pmol/L. The acute administration of AM to humans results in a prompt fall in both blood pressure and vascular resistance.

2. Physiological Functions of Adrenomedullin

 The physiological functions of adrenomedullin are schematically shown in Figure 1B. The normal circulatory concentration of AM in humans is in the range of 2.8 pmol/L. The acute administration of AM to humans results in a prompt fall in both blood pressure and vascular resistance. This occurs because of the stimulation of the second messengers cAMP and cGMP.

In addition to the sharp reduction in the circulatory system’s blood pressure, there is also a fall in peripheral resistance, and reductions in the concentration of angiotensin II and endothelins. In the kidney, administration of AM to humans results in a rapid increase in renal blood flow, renin release, and an increase in the glomerular filtration rate and an increase in the adversary effects of both urinary Na+ excretion and water excretion. The presence of AM in the circulatory system and its adverse effects on the kidney lead to a reduction in the production by angiotensin II and the adrenals zona glomerulosa of aldosterone. As shown in figure 1B under the heading of “Some cell growth effects,” the presence of AM stimulates bone formation and under certain conditions it increases tumor cell proliferation. AM can inhibit apoptosis, cell migration/ mitogenesis, and collagen synthesis. In animal studies, where there was a complete homozygous embryonic knock-out of the gene for adrenomedullin, there was a 100% lethality. In contrast, in the heterozygous AM mice there was an increase in blood pressure mediated by the in vivo production of some circulating level AM.

The conclusion of the scientists is that AM “plays an important role in the regulation of blood pressure.”

Because of combined vascular relaxation, natriuresis, and contraction of plasma volume, the natriuretic peptide system is likely the primary defense against hypervolemia. However, with the discovery of adrenomedulla and the wide array of AM mediated responses, it may be possible eventually to understand and define the contribution of adrenomedulla.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية يضمّ جامعتي العميد والكفيل إلى مشروعي الملف الاستنادي والبوابة العراقية

المجمع العلمي يطلق المشروع التطويري الصيفي لطلبة حفظ القرآن الكريم في كربلاء

المجمع العلمي يُحيي ذكرى شهادة الإمام محمد الجواد (عليه السلام) في بغداد

تكريم إدارات المدارس المشاركة في مسابقة بصائر العلم الوطنية الأولى

المزيد

الآخبار الصحية

طريقة مبتكرة للكشف المبكر عن أمراض القلب والشرايين

منظمة الصحة تحذر من خطر إدمان الشباب لأكياس النيكوتين

خبراء يحذرون من عادة شائعة تهدد صحة الملايين

خبير يكشف 5 حقائق طبية صادمة وغير معروفة

المزيد

الآخبار التكنلوجية

الأولى في العالم.. الصين تجري تجربة رائدة في الفضاء باستخدام "جنين اصطناعي"

دراسة حديثة تفند ربط التستوستيرون بالمخاطرة لدى الرجال

ميتا تضيف وضع "المحادثة المخفية" إلى تطبيق "واتساب"

فوبيا المرتفعات ليست من الدماغ.. دراسة تكشف السبب

المزيد

مواضيع ذات صلة

Hemoglobin

Erythropoietin (the Protein)

Kallikreins and Kinins

Biological Actions of NO

Biological Actions of Endothelins

Red Blood Cell Enzymopathies- Metabolic Pathways

Hemoglobins with Decreased Oxygen Affinity

Chemistry, Biosynthesis, and Secretion of Nitric Oxide System

Chemistry, Biosynthesis, and Secretion of Endothelins

Chemistry, Biosynthesis, and Secretion of ANP

Hemoglobins with Increased Oxygen Affinity

Specific Enzymes are Associated with Compartments Separated by the Mitochondrial Membranes