ADM - Adrenomedullin | Elisa - Clia - Antibody - Protein

Background

Adrenomedullin (ADM) is a peptide hormone that is primarily secreted by various tissues, including the adrenal medulla, vascular endothelium, heart, lungs, and kidneys. Adrenomedullin is a 52-amino acid peptide hormone derived from a larger precursor protein called preproadrenomedullin. It belongs to the calcitonin gene-related peptide (CGRP) family and shares structural similarities with calcitonin and calcitonin gene-related peptide. Adrenomedullin plays a crucial role in regulating vascular tone, blood pressure, and cardiovascular homeostasis by promoting vasodilation and inhibiting vasoconstriction. Additionally, adrenomedullin exhibits anti-inflammatory, anti-apoptotic, and angiogenic properties, contributing to tissue protection and repair.Adrenomedullin binds to specific receptors known as adrenomedullin receptors (ADMR), which are coupled to G proteins. Activation of adrenomedullin receptors leads to the stimulation of intracellular signaling pathways, including cyclic AMP (cAMP) and cyclic GMP (cGMP) pathways, ultimately mediating its physiological effects. Adrenomedullin expression and secretion are regulated by various factors, including hypoxia, inflammation, mechanical stretch, and hormones such as angiotensin II and glucocorticoids. Its expression can be induced in response to stress or pathological conditions to modulate physiological responses and promote tissue adaptation and repair. Dysregulation of adrenomedullin has been implicated in various pathological conditions, including cardiovascular diseases (such as hypertension, heart failure, and atherosclerosis), pulmonary diseases, sepsis, cancer, and kidney disorders

Protein Structure

Adrenomedullin is synthesized as a preprohormone, which undergoes several processing steps:

• Preproadrenomedullin: The initial 185-amino acid precursor.
• Proadrenomedullin: After removal of the signal peptide, the 164-amino acid prohormone is formed.
• Mature Adrenomedullin: Further processing yields the active 52-amino acid peptide.

Key structural features include:

• Amino Terminus: Contains a signal peptide for secretion.
• Ring Structure: A six-amino acid ring formed by a disulfide bond is crucial for its activity.
• C-terminal Amidation: Essential for full biological activity.

Classification and Subtypes

Adrenomedullin belongs to the calcitonin gene-related peptide (CGRP) family, which includes:

• Adrenomedullin (ADM)
• Adrenomedullin 2/Intermedin (ADM2/IMD)

Function and Biological Significance

Adrenomedullin is a versatile hormone with several key functions:

1. Vasodilation: ADM induces vasodilation by stimulating nitric oxide (NO) production and activating adenylate cyclase, leading to increased cAMP levels in vascular smooth muscle cells.
2. Angiogenesis: Promotes the formation of new blood vessels, enhancing tissue perfusion and repair.
3. Cardioprotection: Protects against myocardial ischemia and reperfusion injury, reduces cardiac fibrosis, and improves cardiac function.
4. Fluid and Electrolyte Balance: Regulates renal function by promoting natriuresis and diuresis.
5. Anti-inflammatory Effects: Reduces the production of pro-inflammatory cytokines and modulates immune responses.

Interactions

Adrenomedullin exerts its effects through interactions with specific receptors and signaling pathways:

Receptors:

• Calcitonin Receptor-Like Receptor (CRLR): Forms a complex with receptor activity-modifying proteins (RAMP2 or RAMP3) to create functional ADM receptors.

Signaling Pathways:

• cAMP Pathway: Activation of adenylate cyclase increases cAMP levels, leading to vasodilation and other downstream effects.
• NO Pathway: Stimulates endothelial nitric oxide synthase (eNOS), enhancing NO production and promoting vasodilation.
• MAPK Pathway: Involvement in cellular growth, survival, and angiogenesis.

Clinical Significance

1. Cardiovascular Diseases: Elevated ADM levels are associated with heart failure, hypertension, and atherosclerosis. ADM's vasodilatory and cardioprotective properties make it a potential therapeutic target.
2. Sepsis and Septic Shock: ADM has been implicated in the pathophysiology of sepsis, with elevated levels correlating with disease severity and outcomes. Therapeutic modulation of ADM may improve sepsis management.
3. Pulmonary Diseases: ADM plays a role in pulmonary hypertension and chronic obstructive pulmonary disease (COPD) by modulating pulmonary vascular tone and inflammation.
4. Cancer: ADM promotes angiogenesis and tumor growth, making it a potential target for anti-cancer therapies.

Summary

Adrenomedullin (ADM) is a multifunctional peptide hormone involved in vasodilation, angiogenesis, cardioprotection, and regulation of fluid and electrolyte balance. It is synthesized as a preprohormone and processed to an active 52-amino acid peptide. ADM interacts with receptors such as CRLR in combination with RAMP2 or RAMP3, activating signaling pathways like cAMP and NO to exert its effects. Clinically, ADM is significant in cardiovascular diseases, sepsis, pulmonary diseases, and cancer. Its diverse biological functions and potential as a therapeutic target make it an important focus in medical research.