A. AVP Receptors

There are three AVP receptors, V1a, V1b, and V2, each encoded by a separate gene and each with distinct tissue distribution, signal transduction pathways, and biological consequences. Some of the distinguishing characteristics of these members of the rhodopsin family of the G-protein coupled receptor (GPCR) superfamily are shown in Table 1. The secondary structure of VP2, the form in the renal nephron, is shown in Figure1. Both V1 subtypes stimulate Gq11 leading to the activation of phospholipase C and breakdown of phosphoinositides, whereas the V2 receptor activates, through Gs, adenylate cyclase and followed by cAMP activation of PKA. V1a is fairly widely distributed and has a vari ety of functions in the vasculature and elsewhere. The localizations of the other two vasopressin receptors are more restricted. V2 in the kidney is responsible for the primary physiological effect of vasopression, water resorption, giving the hormone its other name, antidiuretic hormone. The V1b receptor, located mainly in the anterior pituitary corticotrophs, is known primarily for its effect on ACTH secretion, but has been found out side the pituitary where its functions have not yet been delineated.

Table1. Distribution and Activity of AVP Receptors

Fig1. The secondary structure of the V2 receptor for arginine vasopressin. Residues shown in red are positions of mutations leading to diabetes insipidus, the primary clinical manifestation of lack of AVP.

B. AVP Regulation of Water Handling

The primary action of arginine vasopressin (AVP), also known as antidiuretic hormone, is the inhibition of water diuresis (loss of water in the urine), mediated by AVP V2 receptors in the distal nephrons of the kidney. AVP also elevates blood pressure and constricts coronary arteries as described in the following section.

Figure 2 shows an overview of the main features of water balance. The hypothalamic osmoreceptor detects elevations in serum tonicity reflecting low blood volume. The vasopressinergic neuron receives the signal and transmits it to its own nerve ending for the release of vasopressin (AVP) and neurophysin. AVP binds to a membrane receptor located in distal tubular cells of the kidney, and, through cAMP and PKA, aquaporin-2 is phosphorylated and translocated to the cell apical membrane of the distal nephron. The increase in water channels in renal cells results in increased movement of water from urine through the renal cell into blood. The net increase in blood pressure and lowered osmolality results in a quenching of the signal to the vasopressinergic neuron. The increased serum tonicity that activates the AVP pathway also signals the hypothalamic thirst center, which is closely associated with the osmoreceptor. Consequently, more water is consumed, which leads to the dilution of body fluids. Simultaneously, the kidney has sensed increased Na+ concentration in the blood, which inhibits the Na+ conservation mechanism and results in the excretion of Na+, which in turn tends to reduce blood pressure. Thus, these two systems function to maintain homeostatic water balance in the body.

Fig2. Role of AVP in the regulation of water balance and plasma tonicity. Changes in plasma tonicity are detected by the hypothalamic osmoreceptors, leading to changes in AVP. The responses to increased tonicity (decreased water and volume) are shown on the left and those in response to decreased tonicity (increased water and volume) are on the right.

C. Cardiovascular Effects of AVP

AVP acts on the smooth muscle cells of the vasculature through its receptor V1a (Table 1). The sensitivity of these cells to AVP, and therefore its vasopressor activity, varies with location with splanchnic, hepatic, and renal vessels being the most responsive at physio logical concentrations of the hormone.

D. Effects of AVP on Glucose Homeostasis

Glycogenolysis is stimulated by AVP in the liver through the mobilization of intracellular stores of Ca2+ (from mitochondria and/or endoplasmic reticulum) by the ligand-activated receptor V1a. Increased cytosolic Ca2+ stimulates phosphorylase b kinase and, hence, phosphorylase a activation through phosphorylation. AVP also alters the phosphorylation and therefore the activation state of a dozen or so other intracellular liver proteins including pyruvate kinase.

E. Effects of AVP on ACTH Secretion

A subpopulation of the hypothalamic neurons that express and secrete corticotrophic releasing hormone (CRH) also synthesize and co-secrete AVP. In these neurons, the amounts of both AVP and CRH are inversely related to glucocorticoid levels, suggesting that they are both subject to feedback inhibition. In humans, infusion of the anterior pituitary with AVP alone has little effect on ACTH secretion, but its effect is synergistic with that of CRH. As indicated in Table 1, this biological effect of AVP is mediated by the receptor V1b, which is distinct from the CRH receptor.

F. AVP and the Brain

 CNS neural networks that are anatomically and functionally separate from the neurohypophysis con tain vasopressinergic neurons. In many mammalian species these central AVP actions play important roles in social and reproductive behavior. In general AVP tends to mediate male behaviors while oxytocin mediates those associated with female aspects of repro duction (see section V following). For example, in the monogamous male prairie vole, AVP plays a role in pair bonding. In the Brattleboro rat, which has a spontaneous mutation in the AVP gene, social recognition memory is impaired due to the lack of functional AVP. Information is beginning to emerge to indicate that these pathways, which utilize the V1a receptor, operate in humans as well. For example, genetic association studies suggest a relationship between structural variations in the V1a gene and behavioral patterns such as autism spectrum disorder and social phobias.

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متى يصبح محيط الخصر "مؤشر خطر"؟

دراسة تكشف دور "العوامل الوراثية" في تحديد عمر الإنسان

رائحة كريهة في الجسم.. "علامة خفية" أخطر مما تتصور

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مواضيع ذات صلة

GHD with Accompanying Features

Structures of Oxytocin and Vasopressin

Syndrome of Inappropriate Antidiuresis

Hypothalamic Diabetes Insipidus

The Physiology of oxytocin (OT)

Regulation and Biological Actions of Growth Hormone and Prolactin

Hypothalamic Control of Growth Hormone Secretion

Corticotropin-Releasing Hormone

The Physiology of Vasopressin

Gonadotropin-Releasing Hormone

Thyrotropin-Releasing Hormone

Biosynthesis of Adrenal Cortex Mineralocorticoids, Glucocorticoids, and Some Androgens