Vasopressin receptor increased

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. 

Inhibition of V2 vasopressin receptors causes an increase in urine volume primarily by reducing the re-absoiption of water along the collecting duct, an aquaretic effect that is fundamentally different from the natriuretic actions discussed so far. Nevertheless, some of the conditions calling for the use of natriuretic intervention are identical to those in which the administration of a new class of orally active nonpeptide V2 antagonists may be useful (tolvaptan, lixivaptan, and others). 

Several nonpeptidic, orally active vasopressin receptor antagonists have been developed. The dual V1A/V2R antagonist conivaptan is used in the treatment of hyponatraemia and could also become useful for diseases such as congestive heart failure, in which increased peripheral resistance and dilutional hyponatremia both are present [4]. Side effects of conivaptan include headache, injection site reactions, vomiting, diarrhoea, constipation and thirst. 

CRH probably does not act alone. According to clinical neuroendocrinology, vasopressin is a prime candidate for the synergy of CRH effects at pituitary CRHj receptors, and it also has behavioral effects that are compatible with a role in depression. Chronic psychosocial stress enhances vasopressin expression and increases the number of hypothalamic neurons coexpressing CRH and vasopressin. Infusion of an antisense oligodeoxy-nucleotide, which corresponds to the mRNA of vasopressin type 1 receptor, into the septum led to reduced anxiety-related behavior that parallels decreases in vasopressin receptor binding (Landgraf et al. 1995). 

Three subtypes of vasopressin receptors have been identified. Via receptors mediate the vasoconstrictor action of vasopressin Vib receptors potentiate the release of ACTH by pituitary corticotropes and V2 receptors mediate the antidiuretic action. Via effects are mediated by activation of phospholipase C, formation of inositol trisphosphate, and increased intracellular calcium concentration. V2 effects are mediated by activation of adenylyl cyclase. 

Due to the dual renal and vascular action of AVP, scientists at Yamanouchi Pharmaceuticals became interested in the identification of dual Vla/V2 vasopressin receptor antagonists, particularly because such agents were anticipated to be of unique utility in the treatment of congestive heart failure (CHF), where aberrant AVP secretion appeared responsible for both the onset of hypervolemic hyponatremia and deleterious increases in vascular resistance.14 The resulting drug discovery program ultimately lead to the identification of conivaptan HCl (1). 

Conivaptan HCl (1) is a potent dual Vla and V2 vasopressin receptor antagonist that increases water excretion without significant electrolyte depletion. 

Vasopressin bind to human platelets via V, vasopressin receptors and mediates activation of the polypho hoinositol metabolism via PLC, increase in [Ca ]j and aggregation (Pollock and MacMtyre, 1986 hiaba et al, 1988). 

Nephrogenic Diabetes Insipidus. Failure of the kidney to respond to normal or increased concentrations of AVP can cause NDI. In the majority of these patients, AVP is mcapable of stimulating cychc adenosine monophosphate (cAMP) formation. Two causes have been described for this disorder (1) mutation in the vasopressin receptor and (2) mutations in the aquaporin-2 water channels. Hie vasopressin receptor mutation form of NDI is an X-chromosome-linked disorder that mostly affects males. Females are more likely to have the aquaporin-2 water channel gene defect on chromosome 12,ql2-13, which produces an autosomal recessive disease. Acquired forms of NDI may be caused by metabolic disorders (hypokalemia, hypercalcemia, and amyloidosis), drugs (hthium, demeclocycline, and barbiturates), and renal diseases (polycystic disease and chronic renal failure). NDI may also be seen in the absence of these factors (idiopathic). 

Hensen J, Haenelt M, Gross P. Water retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors. Eur J Endocrinol 1995 132 459-464. 

Answer C. Neurogenic diabetes insipidus is treated with desmopressin, a drug that is similar to vasopressin (ADH) but a selective activator of V2 receptors in the kidney. Remember that V, receptors are present in smooth muscle, and their activation leads to vasoconstriction and bronchoconstriction. Nephrogenic diabetes insipidus (decreased response of vasopressin receptors) is treated with thiazides except in the case of that induced by lithium, when amiloride is preferred (because thiazides increase blood levels of lithium). 

Vasopressin analogs with longer duration of action and selectivity for vasopressin receptor sub-types (Vj Vi. Vj vasopressin receptors, which mediate pressor responses and antidiuretic responses, respectively) have been synthesized. The V -selective agonist, l-deamino-8-D-arginine vasopressin, also called desmopressin (DDAVP), has -3000 times greater antidiuretic-to-vasopressor ratio than vasopressin and is the preferred drug for the treatment of central diabetes insipidus. Substitution of Val for Gin in position 4 further increases the antidiuretic selectivity, and the antidiuretic-to-vasopressor ratio for deamino [Val", D-Arg ]AVP is -11,000 times greater than vasopressin. 

Increasing Vj selectivity has been more difficult than increasing selectivity. Vasopressin receptors in the adenohypophysis that mediate vasopressin-induced ACTH release are neither classical Vj nor Vj receptors. Since the vasopressin receptors in the adenohypophysis appear to share a common signal-transduction mechanism with classical Vj receptors, and since many vasopressin analogs with vasoconstrictor activity release ACTH, Vj receptors have been subclassified into Vj (vascular/hepatic) and Vjj (pituitary) receptors. Vjj receptors also are called Vj receptors. Vasopressin analogs that are selective agonists for Vj and Vjj receptors have been synthesized but are not available clinically. 

Electrolyte balance The increase in serum sodium concentration after the start of therapy with vasopressin receptor antagonists can be rapid [79 ]. 

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