Diuretic peptides

Until recently, stimulants and narcotics were the most sought drugs in athletics. To circumvent the rules, drugs that do not affect the mood find now large use, like substances that increase the red blood cells count (blood doping), diuretics, peptide hormones, beta-blocker, and anabolic steroids. 

Diuretic peptides promote diuresis in insects in different ways. The chapter reviews the isolation and chemical identification of diuretic peptides from three insects Locusta migratoria, Manduca sexta, and Acheta domesticus. The biological activities of the characterized peptides are discussed. 

Mordue s group isolated and partially characterized a diuretic peptide from the corpora cardiaca (CC) of Locusta migratoria (4.) Batches of up to 150 CC were collected and extracted with 20% aqueous methanol. After centrifugation,... 

Rafaeli et ai. have recently reported the existence of an adrenocorticotropin (ACTH)-like material in locust CC (5.) detectable by immunoassay. They also reported that ACTH at 10 mM stimulated liquid excretion from, and elevated levels of cAMP in, locust Malpighian tubules. Extracts of CC produced similar effects in the traditional in vitro assay (fi.). They believe that a diuretic peptide in locusts has at least immunological similarity to ACTH. While the partial sequence reported (4.) by Morgan et ai. has no apparent similarity to ACTH, it is conceivable that these groups could be investigating the same factor. 

Only one of the four reports on characterization of diuretic peptides relied on a direct assay of the effects of extracts on Malpighian tubules (2 S.). A more common strategy has been the use of a less laborious bioassay. 

Insect diuretic peptides, two structurally distinct families of diuretic peptides (DP) that stimulate primary urine production by insect Malpighian tubules and regulate water loss from the excretory system. CRH-related diuretic peptides and insect kinins have been found in a number of species, and they may be ubiquitous in insects. CRH-related diuretic peptides belong to the vertebrate CRH/sauvagine/urotensin I/urocortin... 

Natriuretic Peptide Diuretics. Atrial natriuretic peptide (ANP), an endogenous diuretic, natriuretic, and vasodilator, is a peptide hormone primarily synthesized and stored by atrial cardiocytes, and secreted by the atria in response to mechanical stretch of the atria. It was discovered in the cmde extracts of atria in 1981 (51). ANP is also known as anaritide [95896-08-5] atrial natriuretic factor [104595-79-1] (ANF) auriculin ... 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Anti-diuretic hormone is a small peptide shown as Figure 8.9, which is secreted by the pituitary gland located at the base of the brain. The cellular actions of ADH are mediated by activation of a G-protein linked receptor generating cAMP as second messenger. Absence of ADH or a functional defect in the action of ADH-stimulated water reabsorption in the collecting duct results in the condition diabetes insipidus, characterized by the passing of large volumes (= diabetes) of dilute (= insipidus) urine. 

ANP now belongs to a family of natrinreteic peptides that also includes BNP (brain natrinretic peptide) and CNP (C-type natriuretic peptide). BNP and CNP have different N- and C-termini to ANP. CNP has a shorter N-terminal than either ANP or BNP. CNP has less natriuretic and diuretic activity than ANP or BNP. 

The atria and other tissues of mammals contain a family of peptides with natriuretic, diuretic, vasorelaxant, and other properties. The family includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). The peptides share a common 17-amino-acid disulfide ring with variable C- and N-terminals (Figure 17-5). A fourth peptide, urodilatin, has the same structure as ANP with an extension of four amino acids at the N-terminal. 

BNP was originally isolated from porcine brain but, like ANP, it is synthesized primarily in the heart. It exists in two forms, having either 26 or 32 amino acids (Figure 17-5). Like ANP, the release of BNP appears to be volume-related indeed, the two peptides may be cosecreted. BNP exhibits natriuretic, diuretic, and hypotensive activities similar to those of ANP but circulates at a lower concentration. 

Atrial Natriuretic Peptide Potentiator Diuretics. Neural endopeptidase inhibitors or atrial peptidase inhibitors are compounds that inhibit the enzyme (hat degrades ANP. resulting in higher plasma concemratioas, and longer duration of action, of ANP. The diuretic effects of this class... 

Atrial natriuretic peptide (ANP) Several active peptides cleaved from precursor polypeptide of 126 residues Smooth muscle relaxation diuretic activity... 

Minocycline, 200 mg orally daily for 5 days, can eradicate the meningococcal carrier state, but because of side-effects and resistance of many meningococcal strains, rifampin is preferred. Demeclocycline inhibits the action of ADH in the renal tubule and has been used in the treatment of inappropriate secretion of ADH or similar peptides by certain tumors (see Chapter 15 Diuretic Agents). 

NG Delaney, EN Gordon, JM DeForrest, DW Cushman. Amino acid and peptide derivatives as inhibitors of neutral endopeptidase and their use as antihypertensives and diuretics. European Patent EP361365, 1988. 

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