Kidney peptide hormones

Natriuretic peptides are a family of peptide hormones. All of them contain a 17-amino acid long ring that is closed by a disulfide bond between two cysteine residues. ANP (atrial natriuretic peptide) is mainly expressed in the atria of the heart, whereas BNP (B-type natriuretic peptide) is synthesized in the ventricular myocardium. CNP occurs mainly in the endothelium and is thought to have a paracrine function. ANF and BNF lower blood pressure by a direct effect on smooth muscle and on the salt retention in the kidney. Natriuretic peptides bind and activate particulate guanylyl cyclases. 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

The other hormone of note synthesized by kidney is erythropoietin (EPO), a glycosylated peptide hormone (molecular weight approximately 50 000), which promotes red blood cell formation and is secreted in response to poor oxygen perfusion (hypoxia) of the kidney. This, along with the control of blood pressure via the RAA system illustrates the importance of the kidney in regulating aspects of the blood vascular system. Further details of EPO can be found in Chapter 5. 

The peptide hormone parathyrin (PTH), which is produced by the parathyroid gland, stimulates Ca "" resorption in the kidneys and at the same time inhibits the resorption of phosphate. In conjunction with the effects of this hormone in the bones and intestines (see p. 344), this leads to an increase in the plasma level of Ca and a reduction in the level of phosphate ions. 

Erythropoietin is a peptide hormone that is formed predominantly by the kidneys, but also by the liver. Together with other factors known as colony-stimulating factors" (CSF see p.392), it regulates the differentiation of stem cells in the bone marrow. 

The peptide hormone angiotensin II is not synthesized in a hormonal gland, but in the blood. The kidneys take part in this process by releasing the enzyme renin. 

Degradation of peptide hormones often starts in the blood plasma or on the vascular walls it is particularly intensive in the kidneys. 

PEPTIDE HORMONES OF THE KIDNEY (RENIN-ANGIOTENSIN SYSTEM)... 

Natriuretic Peptide Diuretics. Atrial natriuretic peptide (ANP). an endogenous diuretic, natriuretic, and vasodilator, is a peptide hormone primarily synthesized and stored hy atrial cardiocytes. and secreted hy the atria in response to mechanical stretch of the atria. ANP is also known as anarilide. CiijHnsNjoO.ijS-i atrial natriuretic factor (ANF) auricuiin cardionairin and alriopeptide. Its primary action Is in the kidney and the vascular system. 

Antidiuretic hormone is a posterior pituitary peptide hormone that binds to vasoconstrictive Via receptors (via Gaq to activate PLC and thence increase cytsosolic Ca2+), to V2 receptors (causing kidney water reabsorption via Gas and increased cAMP) and to corticotropin secretion-regulating Vlb (V3) receptors (mediated by Gaq to activate PLC and thence increase cytosolic Ca2+). For bioactive-G protein interactions see Table 5.9. 

Q4 The parathyroids produce a peptide hormone, PTH, which controls the level of calcium in the body. A sensor on the surface of the parathyroid cells monitors blood calcium concentration and PTH is secreted in response to a fall in plasma calcium ion concentration. An increase in the level of PTH leads to hypercalcaemia (raised blood calcium) conversely, a reduction in the level of PTH leads to hypocalcaemia. PTH acts on the kidney to reduce reabsorption of phosphate and at the same time to increase reabsorption of calcium. In addition, it promotes the release of calcium and phosphate into the blood by activating osteoclasts, which break down the inorganic matrix of bone. PTH also increases the absorption of calcium by the mucosal cells of the intestine. The latter is a rather slow, indirect action mediated by PTH stimulation of calcitriol secretion by the kidney. 

Naturally occurring peptides, typically below the kidney size cut-off and, hence, usually collected from urine or from blood hemodialysate, provide a complementary picture of many events at the low-mass end of the plasma proteome. It provides a large source of proteins and peptides below 45 kDa. Such material has been analyzed by combined chromatography and MS approaches to resolve -5000 different peptides, including fragments of 75 different proteins [60]. Of the fragments, 55% percent were derived from plasma proteins, and 7% of the entries represented peptide hormones, growth factors, and cytokines. 

Calcitonin is a peptide hormone produced by the C cells of the thyroid gland (in mammals). It acts on bone (inhibiting osteoclasis) to reduce the rate of bone turnover, and on the kidney to reduce reabsorption of calcium and phosphorus. It is obtained from natural sources (pork, salmon, eel), or S3mthesised. The t/ varies according to source t/ human is 10 min. Antibodies develop particularly to pork calcitonin and neutralise its effect synthetic salmon calcitonin (salcatonin) is therefore preferred for prolonged use loss of effect may also be due to down-regulation of receptors. Calcitonin is used (s.c., i.m. or intranasally) to control hypercalcaemia (rapid effect), Paget s disease of bone (relief of pain, and to relieve compression of nerves, e.g. auditory cranial), metastatic bone cancer pain, and postmenopausal osteoporosis. 

AVP is a pituitary peptide hormone that plays an important role in regulation of renal water and solute excretion. AVP secretion is linked directly to changes in plasma osmolality, thus attempting to maintain body fluid homeostasis. The physiologic effects of AVP are mediated through the Via and V2 receptors. Via receptors are located in vascular smooth muscle and in myocytes, where their stimulation by AVP results in vasoconstriction and increased cardiac contractility, respectively. V2 receptors are located in the collecting duct of the kidney, where AVP stimulation causes reabsorption of free water. 

Hypertension is an increase of blood pressure to levels greater than normal that arises because of a mismatch between the volume of the vascular tree and the volume of blood. Blood volume depends on total body sodium content, which is a balance between sodium intake and output. Total body sodium is controlled by variable excretion of sodium by the kidneys. To regulate sodium balance, the primary variable that the kidney monitors is not total body sodium but rather systemic blood pressure. Renal regulation of blood pressure is via the release of the peptide hormone renin from specialized renal cells. Release of rerun ultimately leads to the production of angiotensin H. Angiotensin II increases total peripheral resistance and blood pressure and also leads to an increase in aldosterone. Aldosterone is a steroid... 

Peptide hormones are produced by the endocrine glands (pituitary, thyroid, pineal, adrenal, and pancreas) or by various organs such as the kidney, stomach, intestine, placenta, or liver (Table 3.4). Peptide hormones can have complex, convoluted structures with hundreds of amino acids. Figure 3.2 illustrates the chemical structure of human insulin and its three-dimensional shape. Insulin is made of two amino acid sequences. The A-Chain has 21-amino acids, and the B-Chain has 30-amino acids. The chains are linked together through the sulfur atoms of cysteine (Cys). Peptide hormones are generally different for every species, but they may have similarities [11]. Human insulin is identical to pig insulin, except that the last amino acid of the B-Chain for the pig is alanine (Ala) instead of threonine (Thr) (lUPAC and lUBMB) [9] and [11]. 

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