Urodilatin
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Urodilatin (URO) is a
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...
that causes natriuresis by increasing
renal blood flow In the physiology of the kidney, renal blood flow (RBF) is the volume of blood delivered to the kidneys per unit time. In humans, the kidneys together receive roughly 25% of cardiac output, amounting to 1.2 - 1.3 L/min in a 70-kg adult male. It ...
. It is secreted in response to increased
mean arterial pressure In medicine, the mean arterial pressure (MAP) is an average blood pressure in an individual during a single cardiac cycle. MAP is altered by cardiac output and systemic vascular resistance. Testing Mean arterial pressure can be measured dire ...
and increased blood volume from the cells of the
distal tubule The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen ...
and
collecting duct The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in elect ...
. It is important in oliguric patients (such as those with
acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are c ...
and
chronic kidney failure Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
) as it lowers serum
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...
and increases
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...
output.


Interactions

Atrial natriuretic peptide Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/p ...
(CDD/ANP-99-126) is a hormone system of clinical importance. Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from CDD/ANP-99-126, which is excreted into the circulation via exocytosis. The prototype of the natriuretic hormones is cardiodilatin /
atrial natriuretic peptide Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/p ...
(CDD/ANP). The endocrine heart is composed of specific myoendocrine cells that synthesize and secrete the natriuretic peptide hormones, which exhibit
diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...
and
vasorelaxant Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...
properties; secretion is the basis for a
paracrine Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over ...
system regulating water and
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...
reabsorption In renal physiology, reabsorption or tubular reabsorption is the process by which the nephron removes water and solutes from the tubular fluid (pre-urine) and returns them to the circulating blood. It is called ''reabsorption'' (and not ''absorp ...
. Research efforts since the early 1980s have studied their effects on electrolyte
homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
. When administered intravenously, urodilatin induces strong
diuresis Diuresis () is increased urination (polyuria) or, in the related word senses more often intended, the physiological process that produces such an increase or the administration of medications to encourage that process. It involves extra urine pr ...
and
natriuresis Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldosterone. Natriuresis lowers t ...
with tolerable
hemodynamic Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously mo ...
side effects. Urodilatin is localized in the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
, differentially processed (involved in the regulation of body fluid volume and water-electrolyte excretion, while circulating), and secreted into the urine. As a consequence, urodilatin is involved in drug development along with the
prohormone A prohormone is a committed precursor of a hormone consisting of peptide hormones synthesized together that has a minimal hormonal effect by itself because of its expression-suppressing structure, often created by protein folding and binding additi ...
CDD/ANP-1-126 and cardiodilatin CDD/ANP-99-126. A message for the
preprohormone A preprohormone is the precursor protein to one or more prohormones, which are in turn precursors to peptide hormones. In general, the protein consists of the amino acid chain that is created by the hormone-secreting cell, before any changes have ...
is transcribed in the heart and kidneys from the gene of NP type A, resulting in a cGMP-dependent signal transduction, which induces diuresis and natriuresis, differentially processed to a peptide of 32
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s from the same precursor as renal ANP, may not be identical to the circulating cardiac hormone ANP. The kidneys produce their own natriuretic 32-residue peptide. Urodilatin renal natriuretic peptide potency equals or exceeds that of
Atriopeptin Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/pa ...
NP-(99-126) the prototype of cardiodilatin. Atriopeptin is only of trivial importance in the regulation of sodium excretion during normal living conditions. Urodilatin is little affected by renal enzymes that inactivate
atriopeptin Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/pa ...
, as the kidney elutes with urodilatin rather than with ANP. The degradation rates of (
125I Iodine-125 (125I) is a radioisotope of iodine which has uses in biological assays, nuclear medicine imaging and in radiation therapy as brachytherapy to treat a number of conditions, including prostate cancer, uveal melanomas, and brain tumors. ...
)-urodilatin and 25IANP by pure recombinant NEP (rNEP) were compared.
Phosphoramidon Phosphoramidon is a chemical compound derived from cultures of '' Streptomyces tanashiensis''. It is an inhibitor of the enzyme thermolysin, of the membrane metallo-endopeptidase, Urodilatin has a four-residue extension at the N-terminus neutral endopeptidase-24.11 (NEP) plays a physiological role in metabolizing
atrial natriuretic peptide Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/p ...
, and C-type natriuretic peptide (
prohormone A prohormone is a committed precursor of a hormone consisting of peptide hormones synthesized together that has a minimal hormonal effect by itself because of its expression-suppressing structure, often created by protein folding and binding additi ...
) degraded the bioactive peptides at about half the rate though the
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
that compete with natriuretic peptides for
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...
by neutral endopeptidase.


References

{{reflist Hormones of the kidneys Peptides