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Purinergic receptors and renin

Bellamkonda K Kishore, Simon C Robson, Karen M Dwyer
Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis...
June 2018: Purinergic Signalling
Caroline Sunggip, Akiyuki Nishimura, Kakeru Shimoda, Takuro Numaga-Tomita, Makoto Tsuda, Motohiro Nishida
Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Robert I Menzies, Amelia R Howarth, Robert J Unwin, Frederick W K Tam, John J Mullins, Matthew A Bailey
Chronic activation of the renin-angiotensin system promotes hypertension, renal microvascular dysfunction, tissue hypoxia, and inflammation. Despite similar hypertension, an injurious response to excess angiotensin II is greater in F344 than in Lewis rats; the latter displaying renoprotection. Here we studied whether p2rx7, encoding the P2X7 receptor (P2X7R), is a candidate gene for the differential susceptibility to vascular dysfunction under high angiotensin II tone. A 14-day infusion of angiotensin II into F344 rats increased blood pressure by about 15 mm Hg without inducing fibrosis or albuminuria...
November 2015: Kidney International
O Monfredi, M R Boyett
Sick sinus syndrome remains a highly relevant clinical entity, being responsible for the implantation of the majority of electronic pacemakers worldwide. It is an infinitely more complex disease than it was believed when first described in the mid part of the 20th century. It not only involves the innate leading pacemaker region of the heart, the sinoatrial node, but also the atrial myocardium, predisposing to atrial tachydysrhythmias. It remains controversial as to whether the dysfunction of the sinoatrial node directly causes the dysfunction of the atrial myocardium, or vice versa, or indeed whether these two aspects of the condition arise through some related underlying pathological mechanism, such as extracellular matrix remodeling, i...
June 2015: Journal of Molecular and Cellular Cardiology
Silvia Aldi, Alice Marino, Kengo Tomita, Federico Corti, Ranjini Anand, Kim E Olson, Aaron J Marcus, Roberto Levi
Ischemia/reperfusion (I/R) elicits renin release from cardiac mast cells (MC), thus activating a local renin-angiotensin system (RAS), culminating in ventricular fibrillation. We hypothesized that in I/R, neurogenic ATP could degranulate juxtaposed MC and that ecto-nucleoside triphosphate diphosphohydrolase 1/CD39 (CD39) on MC membrane could modulate ATP-induced renin release. We report that pharmacological inhibition of CD39 in a cultured human mastocytoma cell line (HMC-1) and murine bone marrow-derived MC with ARL67156 (100 µM) increased ATP-induced renin release (≥2-fold), whereas purinergic P2X7 receptors (P2X7R) blockade with A740003 (3 µM) prevented it...
January 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
M M Rabadi, H T Lee
One of the frequent clinical complications that results in billions of dollars in healthcare costs annually in the United States is acute kidney injury (AKI). Ischaemia reperfusion (IR) injury is a major cause AKI. Unfortunately, no effective treatment or preventive measure for AKI exists. With increased surgical complexity coupled with increasing number of elderly, the incidence of AKI is becoming more frequent. Adenosine is a metabolic breakdown product of adenosine triphosphate (ATP) and contributes to the regulation of multiple physiological events...
January 2015: Acta Physiologica
E Mironova, N Boiko, V Bugaj, V Kucher, J D Stockand
Discretionary control of Na(+) excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine-tuned in the aldosterone-sensitive distal nephron by the activity of the epithelial Na(+) channel (ENaC). Here, ENaC functions as a final effector of the renin-angiotensin-aldosterone system (RAAS) during negative feedback control of blood pressure. Mutations affecting ENaC activity and abnormal regulation of this channel affect blood pressure through pathological changes to Na(+) excretion...
January 2015: Acta Physiologica
Geoffrey Burnstock, Louise C Evans, Matthew A Bailey
The involvement of purinergic signalling in kidney physiology and pathophysiology is rapidly gaining recognition and this is a comprehensive review of early and recent publications in the field. Purinergic signalling involvement is described in several important intrarenal regulatory mechanisms, including tuboglomerular feedback, the autoregulatory response of the glomerular and extraglomerular microcirculation and the control of renin release. Furthermore, purinergic signalling influences water and electrolyte transport in all segments of the renal tubule...
March 2014: Purinergic Signalling
Daniela Patinha, Joana Afonso, Teresa Sousa, Manuela Morato, António Albino-Teixeira
BACKGROUND: Diabetes and hypertension independently contribute to renal injury, and the major mechanisms involved are increased reactive oxygen species (ROS) bioavailability and renin-angiotensin system (RAS) activation. We investigated the role of adenosine in controlling ROS production and RAS activation associated with renal dysfunction in hypertension and diabetes. METHODS: Fourteen days after induction of diabetes with streptozotocin in 12-week-old male Wistar and spontaneously hypertensive (SHR) rats, animals were treated during 7 days with 2-chloroadenosine (CADO group, 5 mg/kg/d), a stable analogue of adenosine, or underwent a sham operation procedure...
March 2014: Upsala Journal of Medical Sciences
Yujun Du, Xiujiang Li, Bin Liu
Cardiorenal syndrome (CRS) is characterized as a syndrome involving both the cardiovascular system and kidneys. Due to its complexity and high mortality, it has becoming a significant burden and a universal clinical challenge to society worldwide. The mechanisms underlying CRS are potentially multifactorial, including hemodynamic alterations, neurohormonal activation, inflammation, oxidative stress, iron disorders, anemia, and mineral metabolic derangements. Despite the understanding and awareness of CRS gaining attention, appropriate approaches to manage CRS remain deficient...
March 18, 2014: Life Sciences
Jian-xin Tan, Xiu-lan Huang, Bo Wang, Xing Fang, Di-nan Huang
OBJECTIVE: Recent studies showed that adenosine played important roles in vasodilation. This study aimed to investigate the effects of adenosine, its A1 and A2b receptor agonists on pulmonary artery hypertension (PAH) induced by chronic hypoxia in rats by continuously subcutaneous administration with an osmotic pump for 14 days, and to see if rennin angiotensin system and inducible nitric oxygen synthase (iNOS)/nitric oxide (NO) mediate the effects. METHOD: Fifty-six male SD rats were randomly assigned to seven groups...
October 2012: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Lingli Li, Diane Mizel, Yuning Huang, Christoph Eisner, Marion Hoerl, Manfred Thiel, Jurgen Schnermann
A(1) adenosine receptors (A1AR) are required for the modulation of afferent arteriolar tone by changes in luminal NaCl concentration implying that extracellular adenosine concentrations need to change in synchrony with NaCl. The present experiments were performed in mice with a null mutation in the gene for the major equilibrative nucleoside transporter ENT1 to test whether interference with adenosine disposition by cellular uptake of adenosine may modify TGF characteristics. Responses of stop flow pressure (P(SF)) to maximum flow stimulation were measured in mice with either C57Bl/6 or SWR/J genetic backgrounds...
February 15, 2013: American Journal of Physiology. Renal Physiology
Tsuneo Takenaka, Tsutomu Inoue, Yoichi Ohno, Takashi Miyazaki, Akira Nishiyama, Naohito Ishii, Hiromichi Suzuki
Previous studies have reported that high-salt intake paradoxically activates tubuloglomerular feedback (TGF) in type 1 diabetes. Using Zucker lean (ZL) and diabetic fatty (ZDF) rats on normal and high-salt diets, renal hemodynamics and the renin-angiotensin system (RAS) were characterized. On normal salt diet, glomerular filtration rate (GFR) was higher in ZDF than ZL rats. Autoregulation of GFR was less efficient and lithium clearance was lower in ZDF rats than ZL rats. Salt load reduced GFR in ZDF rats with restoration of lithium clearance and partial improvement in autoregulatory index (AI)...
September 1, 2012: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Jurgen Schnermann, Josephine P Briggs
The juxtaglomerular (JG) cell product renin is rate limiting in the generation of the bioactive octapeptide angiotensin II. Rates of synthesis and secretion of the aspartyl protease renin by JG cells are controlled by multiple afferent and efferent pathways originating in the CNS, cardiovascular system, and kidneys, and making critical contributions to the maintenance of extracellular fluid volume and arterial blood pressure. Since both excesses and deficits of angiotensin II have deleterious effects, it is not surprising that control of renin is secured by a complex system of feedforward and feedback relationships...
March 2012: Kidney International
Glenn M Toney, Volker Vallon, James D Stockand
PURPOSE OF REVIEW: This review summarizes the new evidence for an intrinsic control system in the aldosterone-sensitive distal nephron in which purinergic signaling regulates sodium transport and governs renal sodium excretion. RECENT FINDINGS: Electrophysiological studies identify epithelial Na(+) channels (ENaC) as final effectors of purinergic signaling via P2Y(2) receptors in the distal nephron. Inhibition of ENaC by autocrine/paracrine purinergic signaling reduces sodium reabsorption allowing an appropriately graded pressure-natriuresis response when delivery of sodium to the distal nephron is high...
January 2012: Current Opinion in Nephrology and Hypertension
Jeffrey J W Verschuren, Stella Trompet, Judith A M Wessels, Henk-Jan Guchelaar, Moniek P M de Maat, Maarten L Simoons, J Wouter Jukema
Pharmacogenetics is the search for heritable genetic polymorphisms that influence responses to drug therapy. The most important application of pharmacogenetics is to guide choosing agents with the greatest potential of efficacy and smallest risk of adverse drug reactions. Many studies focusing on drug-gene interactions have been published in recent years, some of which led to adaptation of FDA recommendations, indicating that we are on the verge of the clinical application of genetic information in drug therapy...
January 2012: European Heart Journal
Peter M T Deen, Joris H Robben
The G protein-coupled succinate and α-ketoglutarate receptors are closely related to the family of P2Y purinoreceptors. Although the α-ketoglutarate receptor is almost exclusively expressed in the kidney, its function is unknown. In contrast, the succinate receptor, SUCRN1, is expressed in a variety of tissues, including blood cells, adipose tissue, liver, retina, and the kidney. Recent evidence suggests SUCRN1 and its succinate ligand are novel detectors of local stress, including ischemia, hypoxia, toxicity, and hyperglycemia...
August 2011: Journal of the American Society of Nephrology: JASN
Volker Vallon, Hartmut Osswald
The autacoid, adenosine, is present in the normoxic kidney and generated in the cytosol as well as at extracellular sites. The rate of adenosine formation is enhanced when the rate of ATP hydrolysis prevails over the rate of ATP synthesis during increased tubular transport work or during oxygen deficiency. Extracellular adenosine acts on adenosine receptor subtypes (A(1), A(2A), A(2B), and A(3)) in the cell membranes to affect vascular and tubular functions. Adenosine lowers glomerular filtration rate by constricting afferent arterioles, especially in superficial nephrons, and thus lowers the salt load and transport work of the kidney consistent with the concept of metabolic control of organ function...
2009: Handbook of Experimental Pharmacology
Francesca Di Sole
PURPOSE OF REVIEW: Intrarenal adenosine is present in the cytoplasm of renal epithelial cells and in the extracellular space. Adenosine is generated at high levels in response to imbalance between energy demand and supply (e.g. increased tubular sodium chloride transport or hypoxia) and activates cell membrane adenosine receptors to affect renal vascular and tubular functions. Adenosine regulates renal sodium and water excretion via a myriad of effects on renal hemodynamic, glomerular filtration rate, renin secretion and direct effects on the renal tubule epithelium...
July 2008: Current Opinion in Nephrology and Hypertension
Fiona Hanner, Julia von Maltzahn, Stephan Maxeiner, Ildiko Toma, Arnold Sipos, Olaf Krüger, Klaus Willecke, János Peti-Peterdi
Connexin (Cx) proteins are known to play a role in cell-to-cell communication via intercellular gap junction channels or transiently open hemichannels. Previous studies have identified several connexin isoforms in the juxtaglomerular apparatus (JGA), but the vascular connexin isoform Cx45 has not yet been studied in this region. The present work aimed to identify in detail the localization of Cx45 in the JGA and to suggest a functional role for Cx45 in the kidney using conditions where Cx45 expression or function was altered...
August 2008: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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