期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 296, 期 2, 页码 R419-R427出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.90784.2008
关键词
aquaporin-2; cAMP; collecting duct; vasopressin; cell volume
类别
资金
- National Institutes of Health [DK56248, DK28602, GM66232]
- O'Brien Kidney Center [P30DK079337]
- American Heart Association [0655232Y]
- [National Kidney Foundation Fellowship]
Rieg T, Vallon V. ATP and adenosine in the local regulation of water transport and homeostasis by the kidney. Am J Physiol Regul Integr Comp Physiol 296: R419-R427, 2009. First published November 19, 2008; doi: 10.1152/ajpregu.90784.2008.-Regulation of body water homeostasis is critically dependent on the kidney and under the control of AVP, which is released from the neurohypophysis. In the collecting duct (CD) of the kidney, AVP activates adenylyl cyclase via vasopressin V(2) receptors. cAMP-dependent activation of protein kinase A phosphorylates the water channel aquaporin-2 and increases water permeability by insertion of aquaporin-2 into the apical cell membrane. However, local factors modulate the effects of AVP to fine tune its effects, accelerate responses, and potentially protect the integrity of CD cells. Nucleotides like ATP belong to these local factors and act in an autocrine and paracrine way to activate P2Y(2) receptors on CD cells. Extracellular breakdown of ATP and cAMP forms adenosine, the latter also induces specific effects on the CD by activation of adenosine A(1) receptors. Activation of both receptor types can inhibit the cAMP-triggered activation of protein kinase A and reduce water permeability and transport. This review focuses on the role and potential interactions of the ATP and adenosine system with regard to the regulation of water transport in the CD. We address the potential stimuli and mechanisms involved in nucleotide release and adenosine formation, and discuss the corresponding signaling cascades that are activated. Potential interactions between the ATP and adenosine system, as well as other factors involved in the regulation of CD function, are outlined. Data from pharmacological studies and gene-targeted mouse models are presented to demonstrate the in vivo relevance to water transport and homeostasis.
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