The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors

Abstract

Juul KV, Bichet DG, Nielsen S, Nørgaard JP. The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors. Am J Physiol Renal Physiol 306: F931-F940, 2014. First published March 5, 2014 doi:10.1152/ajprenal.00604.2013.-The arginine vasopressin (AVP) type 2 receptor (V2R) is unique among AVP receptor subtypes in signaling through cAMP. Its key function is in the kidneys, facilitating the urine concentrating mechanism through the AVP/V2 type receptor/aquaporin 2 system in the medullary and cortical collecting ducts. Recent clinical and research observations strongly support the existence of an extrarenal V2R. The clinical importance of the extrarenal V2R spans widely from stimulation of coagulation factor in the endothelium to as yet untested potential therapeutic targets. These include V2R-regulated membranous fluid turnover in the inner ear, V2R-regulated mitogensis and apoptosis in certain tumor tissues, and numerous other cell types where the physiological role of V2Rs still requires further research. Here, we review current evidence on the physiological and pathophysiological functions of renal and extrarenal V2Rs. These functions of V2R are important, not only in rare diseases with loss or gain of function of V2R but also in relation to the recent use of nonpeptide V2R antagonists to treat hyponatremia and possibly retard the growth of cysts and development of renal failure in autosomal dominant polycystic kidney disease. The main functions of V2R in principal cells of the collecting duct are water, salt, and urea transport by modifying the trafficking of aquaporin 2, epithelial Na ϩ channels, and urea transporters and vasodilation and stimulation of coagulation factor properties, mainly seen with pharmacological doses of 1-desamino-8-D-AVP. The AVPR2 gene is located on the X chromosome, in a region with high probability of escape from inactivation; this may lead to phenotypic sex differences, with females expressing higher levels of transcript than males. vasopressin V 2 receptor; arginine vasopressin V2 receptor; arginine vasopressin; desmopressin; extrarenal vasopressin V 2 receptor THE PURPOSE OF THIS REPORT is to review current evidence on the physiological and pathophysiogical functions of renal and extrarenal arginine vasopressin (AVP) type 2 receptors, referred to as V2Rs (Fig. 1).AVP is an important neurohypophyseal nonapeptide that, via its three receptor types, is primarily responsible for regulating osmotic homeostasis of body fluids, volume homeostasis, and vasoconstriction in addition to an array of central functions such as memory and learning (17,29). In addition to these endocrine functions, AVP also contributes to regulating mitogenesis, cell survival, and death (apoptosis) (77).AVP is released from its storage site in the posterior pituitary (Fig. 2) by highly sensitive osmotic stimuli, specifically by a Ͻ1-2% increase in plasma osmolarity, as originally detailed in the 1940s through classic research by Prof. E. B. Verney (125). AVP release may also ...

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

“…[15][16][17][18][19] Although most of the central actions of vasopressin are mediated via the V1b receptor, some clinical studies have suggested a V2 receptor mediated effect on memory. 20 Therefore, to exclude any possible direct effect of subcutaneously injected dDAVP on behavior, we induced dDAVP-infused normonatremia in rats by injecting dDAVP at 0.7 ng/h and feeding them a high salt, liquid diet formula. Such rats' serum [Na + ] on day 6 was significantly lower than that of control rats, but the difference was extremely small ( Figure 4A); by day 23, however, serum [Na + ] was similar between the two groups ( Figure 4A).…”

Drugs for the treatment of central diabetes insipidus: historical background and modern opportunities

“…Возраст дебюта заболевания зависит от этиологии [48]. [22,23]. АВП кодируется геном AVP-нейрофизина II, синтезируется в супраоп-тическом и паравентрикулярном ядрах гипоталамуса в составе комплекса предшественников АВП, ней-рофизина II и гликопептида копептина, а затем се-кретируется в виде АВП из нейронов в заднюю долю гипофиза.…”

“…АВП кодируется геном AVP-нейрофизина II, синтезируется в супраоп-тическом и паравентрикулярном ядрах гипоталамуса в составе комплекса предшественников АВП, ней-рофизина II и гликопептида копептина, а затем се-кретируется в виде АВП из нейронов в заднюю долю гипофиза. Высвобождение АВП происходит путем кальций-зависимого экзоцитоза в ответ на такие сти-мулы, как ортостатическая гипотензия или рвотный рефлекс [23]. Регуляция водно-электролитного равно-весия с помощью АВП основана на осмоляльности сыворотки крови и объеме циркулирующей крови и осуществляется через рецепторы вазопрессина 2 типа (V2-рецептор) [18,22,23].…”

Arginine Vasopressin Promotes Redistribution of Adhesion Junction Protein E-Cadherin in Kidney Epithelial Cells

“…Recently, several groups from independent labs also demonstrated its involvement in central nervous system that in°uences cognition, memory and aging. 20,21 The most well investigated function of VP in kidney is its e®ect to conserve water by stimulating the expression of aquaporin-2 (AQP2) and regulating cellular distribution of AQP2 in renal collecting duct. 22,23 The release of VP is mostly stimulated by the elevated plasma osmolality; however, the activity of VP under di®erent physical conditions can also be a®ected by the a±nity of the receptors in the target organs as well as the in°uences from other hormones and/or mediators.…”