Hypothalamus vasopressin synthesis

Logically, ADH receptor antagonists, and ADH synthesis and release inhibitors can be effective aquaretics. ADH, 8-arginine vasopressin [113-79-17, is synthesized in the hypothalamus of the brain, and is transported through the supraopticohypophyseal tract to the posterior pituitary where it is stored. Upon sensing an increase of plasma osmolaUty by brain osmoreceptors or a decrease of blood volume or blood pressure detected by the baroreceptors and volume receptors, ADH is released into the blood circulation it activates vasopressin receptors in blood vessels to raise blood pressure, and vasopressin V2 receptors of the nephrons of the kidney to retain water and electrolytes to expand the blood volume. 

Corticotropin-releasing factor and arginine vasopressin, which are released predominantly by the paraventricular nucleus of the hypothalamus, are important regulators of corticotropin (ACTH) release, which in turn triggers the release of cortisol and other steroids by the adrenal gland. Both the administration of certain psychoactive agents and emotional arousal originating from the limbic system are able to modify the functions of the pituitary-adrenal axis and stimulate the synthesis of cortisol. 

The actual site of formation of oxytocin and vasopressin is in the hypothalamus, from which the two peptides are carried to the posterior pituitary bound to neuro-physins (transport proteins) and stored. The structure and synthesis of oxytocin 44 and vasopressin 45 were worked out by du Vigneaud et al. 91... 

Two neuropeptides, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are released from parvoceUular neurons in the hypothalamic PVN to initiate a stress response. The terminal endings of these neurons, located in the median eminence of the hypothalamus, release CRH and AVP into the hypothalamic-hypophysial portal vessel system, where they travel to the anterior pituitary. The two neuropeptides act syn-ergistically on pituitary corticotrophs to activate the synthesis of pro-opiomelanocortin (POMC). This peptide, discussed in detail below, is processed to produce several peptides including adrenocorticotrophic hormone (ACTH), or corticotropin. ACTH released from corticotrophs travels via the bloodstream to act on cells in the zona fasciculata layer of the adrenal cortex, stimulating the synthesis and release of the glucocorticoids, cortisol (in humans) or corticosterone (in rodents). 

The hypothalamus produces vasopressin (VP), oxytocin, and other hormones (mainly peptides and polypeptides) that regulate the synthesis and release of hormones from the anterior pituitary (Table 8-2). 

B. Vasopressin (Antidiuretic Hormone, ADH) Vasopressin is synthesized in the supraoptic nuclei of the hypothalamus and released from the posterior pituitary. As discussed in Chapter 15, vasopressin acts on V2 receptors and increases the synthesis or insertion of water channels by a cAMP-dependent mechanism, resulting in an increase in water permeability in the collecting tubules of the kidney. The increased water permeability permits water reabsorption into the hypertonic renal papilla, thus causing the antidiuretic effect. Vasopressin also causes smooth muscle contraction (a V, effect). Desmopresan, a selective agonist of V2 receptors, is used in the treatment of pituitary diabetes insipidus. 

---