Vasopressins

Vasopressin is a nonapeptide used in the treatment of diabetes insipidus [79], of Alzheimer s disease [80], and in the modulation of blood pressure [81]. Vasopressin is known to be absorbed very poorly after oral administration due to its degradation by proteolytic enzymes. Yamahara et al. [82] have studied the transepithelial 

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The principal hormones of the human posterior pituitary include the two nonapeptides, oxytocin [50-56-6] and arginine vasopressin [11000-17-2] (antidiuretic hormone, ADH). Many other hormones, including opioid peptides (see Opioids, endogenous), cholecystokinin [9011-97-6] (CCK) (see Hormones, BRAIN oligopeptides), and gastrointestinal peptides, also have been located in mammalian neurohypophysis (6), but are usually found in much lower concentrations (7). Studies have demonstrated that oxytocin and vasopressin are synthesized in other human organs, both centrally and peripherally, and there is considerable evidence for their role as neurotransmitters (see Neuroregulators) (8). 

Fig. 1. Stmcture of oxytocin and arginine vasopressin. Numbers indicate approximate location of amino acids sequences found in Table 1. A, oxytocin B,...

Hundreds of analogues of both oxytocin and vasopressin have been synthesized, and the conformations of many of these have been studied (22,23). 

Table 3. Synthetic Analogues of Vasopressin with High Potency or Selectivity...

Table 4. Synthetic Analogues of Oxytocin and Vasopressin Having Antagonist Activities...

Other potential oxytocia antagonists are being developed using leads from naturally occurring, nonpeptide stmctures, such as an extract from Streptomjces (48). A selective nonpeptide vasopressin receptor antagonist also has been found (49). 

Fig. 3. Processing steps of rat and bovine prepro-vasopressin lea ding to the hormone vasopressin and its carrier protein, neurophysin (14). (a) Putative signal peptide (b) vasopressin (c) neurophysin (d) glycopeptide. CHO = carbohydrate.

In humans, the hypothalamic-derived protein and the hormone noncovalent complexes are packaged in neurosecretory granules, then migrate along axons at a rate of 1 4 mm/h until they reach the posterior pituitary where they are stored prior to release into the bloodstream by exocytosis (67). Considerable evidence suggests that posterior pituitary hormones function as neurotransmitters (68) vasopressin acts on the anterior pituitary to release adrenocorticotropic hormone [9002-60-2] (ACTH) (69) as well as on traditional target tissues such as kidneys. Both hormones promote other important central nervous system (CNS) effects (9,70). 

Oxytocin and Vasopressin Receptors. The actions of oxytocin and vasopressin are mediated through their interactions with receptors. Different receptor types as well as different second messenger responses help explain their diverse activities in spite of the hormones stmctural similarities. Thus oxytocin has at least one separate receptor and vasopressin has been shown to have two principal receptor types, and V2. Subclasses of these receptors have been demonstrated, and species differences further compHcate experimental analysis. It is apparent that both oxytocin and receptors function through the GP/1 phosphoHpase C complex (75), while the V2 receptors activate cycHc AMP (76). 

Vasopressin is suppHed as Pitressin Taimate (Parke-Davis) for use as an antidiuretic agent adrninistered intramuscularly (see Diuretic agents). 

Lysine vasopressin is marketed in nasal spray form as an antidiuretic under the trademark Diapid (Sando2). 

D. M. Gash and G. Boer, eds.. Vasopressin Principles and Properties, Plenum, New York, 1987. 

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

ANPs play an important role in the maintenance of cardiovascular homeostasis by counterbalancing the renin—angiotensin (RAS) system. ANP, the main circulating form of the natriuretic peptides, effectively relaxes vascular smooth muscle, promotes the excretion of sodium and water, and in the CNS inhibits vasopressin release and antagonizes AT-II induced thirst. 

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