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Water retention and hyponatremia also occur Post Date: Mon, 13 Oct 2008 13:15:50 +0000 The so-called low-salt syndrome is often encountered in patients continuously receiving potent diuretic agents for the control of hypertension, edema, or the ascites of hepatic cirrhosis (White et al, 1953). Although there is usually no impairment of the patient's neurohypophyseal or renal mechanisms for regulation of osmotic pressure, water is retained in spite of the continuing loss of sodium salts so that plasma osmotic pressure falls below normal It has been suggested that the activation of volume receptors is responsible for the water retention in such patients.Water retention and hyponatremia also occur in patients suffering from certain tumors, most notably bronchial oat-cell carcinoma (the Schwartz-Bartter syndrome). Autor of the post: Undefined It has also been observed Post Date: Mon, 13 Oct 2008 12:59:49 +0000 Such tumors may produce large amounts of an antidiuretic polypeptide, which by all biologi-cal and physical criteria is identical to ADH (Sawyer, 1967a).The above hyponatremic states are examples of what is now referred to as the syndrome of inappro-priate ADH secretion (SIADH), characterized by hyponatremia secondary to decreased free-water excretion in the presence of otherwise-adequate renal function (Bartter and Schwartz, 1967). It has also been observed in association with certain types of pulmonary disease, in traumatic or disease-related brain injury, and during the use of several drugs other than diuretics, such as the oral hypoglycemic agent chlorpropamide (see below). Autor of the post: Undefined In addition to having Post Date: Mon, 13 Oct 2008 12:42:49 +0000 SIADH must be distinguished from pituitary or adrenal insufficiency, hypothyroidism, congestive failure, and so forth, in which hyponatremia may occur due to impairment of the renal capacity for sodium conservation or free-water excretion (Fishman et at, 1971).Chemistry. In addition to having an antidiuretic action, extracts of the neurohypophysis were found to cause vasoconstriction (pressor principle) and to stimulate the smooth muscle of the uterus (oxytocic principle) and the modified smooth muscle of the mammary glands (milk-ejection factor). Autor of the post: Undefined However, by relatively mild procedures Post Date: Mon, 13 Oct 2008 12:24:09 +0000 Extracts further purified to obtain a high ratio of oxytocic to antidiuretic activity have a vasodilator action that is prominent in some species but weak in man. A protein possessing all these properties in the same proportion as crude gland extracts was isolated from the neurohypophysis of oxen (van Dyke et al, 1942). However, by relatively mild procedures it is possible to separate from this protein, neurophysin, the two polypeptides, ADH and oxytocin, that are respon-sible for the biological activity of the extracts (see Table 40-1). Autor of the post: Undefined They appear to be identical Post Date: Mon, 13 Oct 2008 12:12:16 +0000 By a modification of the van Dyke procedure, two closely related proteins, neurophysins I and II, have been identified in extracts of the gland. These have molecular weights of approximately 20,000 and selectively bind one to three molecules of ADH or oxytocin. They appear to be identical to the two proteins found in that fraction of the gland obtained by ultracentrifugation, which contains the neurosecretory granules. Autor of the post: Undefined The structures are shown Post Date: Mon, 13 Oct 2008 11:54:54 +0000 Neurophysin-like proteins that selectively bind ADH or oxytocin have been found in several target organs (uterus, kidney, mammary gland) but not in other tissues studied.duVigneaud and coworkers (1953, 1954) deter-mined the structures of ADH and oxytocin and accomplished the complete synthesis of each. The structures are shown in Figure 40-1,These neurohypophyseal octapeptides are com-mon in all mammals except swine, in which ADH is found to contain lysine in place of arginine. Autor of the post: Undefined Pure, synthetic lysine vasopressin, for Post Date: Mon, 13 Oct 2008 11:42:40 +0000 Therefore, the bovine pituitary, when used as the sole source, supplies hormones identical to those of man. However, most available preparations also contain lysine vasopressin due to the use of porcine as well as bovine pituitaries. Pure, synthetic lysine vasopressin, for which the name lypressin has been adopted, is now available for therapeutic use. Autor of the post: Undefined This substance has the ring Post Date: Mon, 13 Oct 2008 11:28:26 +0000 * Because the activity of the polypeptides has been determined by bioassay procedures that differ somewhat from one laboratory to another, the relative activities shown must be regarded as approximate.An interesting analog, arginine vasotocin, occurs in cer-tain nonmammalian vertebrates. This substance has the ring structure of oxytocin and the side chain of ADH, and has physiological activity in mammals intermediate between that of oxytocin and ADH. Autor of the post: Undefined Removal of the terminal glycine Post Date: Mon, 13 Oct 2008 11:10:55 +0000 It has been found that optimal or near-optimal antidiuretic and oxytocic activities reside in the structures of the naturally occurring hormones of mammals. The intact pentapeptide ring is essential Opening the ring, as well as increasing or decreasing its size by even one carbon atom, causes complete or near-complete loss of activity. Removal of the terminal glycine amide, as by trypsin when the hor-mones are administered orally, also results in inacti-vation. Autor of the post: Undefined For appreciable oxytocic activ-ity, isoleucine Post Date: Mon, 13 Oct 2008 10:51:12 +0000 However, congeners in which this glycine is deamidated usually show increased antidiuretic or oxytocic, but not pressor, activity. A basic amino acid, optimally arginine, in position 8 is essential for antidiuretic activity. For appreciable oxytocic activ-ity, isoleucine in position 3 is critical, as is the length but not the composition of the side chain. 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