ATP, P2 receptors and the renal microcirculation

Abstract

Purinoceptors are rapidly becoming recognised as important regulators of tissue and organ function. Renal expression of P2 receptors is broad and diverse, as reflected by the fact that P2 receptors have been identified in virtually every major tubular/vascular element. While P2 receptor expression by these renal structures is recognised, the physiological functions that they serve remains to be clarified. Renal vascular P2 receptor expression is complex and poorly understood. Evidence suggests that different complements of P2 receptors are expressed by individual renal vascular segments. This unique distribution has given rise to the postulate that P2 receptors are important for renal vascular function, including regulation of preglomerular resistance and autoregulatory behaviour. More recent studies have also uncovered evidence that hypertension reduces renal vascular reactivity to P2 receptor stimulation in concert with compromised autoregulatory capability. This review will consolidate findings related to the role of P2 receptors in regulating renal microvascular function and will present areas of controversy related to the respective roles of ATP and adenosine in autoregulatory resistance adjustments.

ATP as a mediator of macula densa cell signalling

“…In addition, autoregulatory responses were diminished in a P2X 1 receptor knockout mouse. Thus, there is convincing evidence for a role of ATP and purinergic receptors in the process of renal autoregulation (see article by Inscho [81] in this Special Issue).…”

“…The article by Dr. Inscho in this Special Issue [81] eloquently discusses the history of and evidence for a role of ATP in the regulation of renal haemodynamics. The work of this group, as well as studies from the Navar Laboratory at Tulane, set the stage for our contributions in this area [49,[82][83][84][85][86][87][88].…”

“…This has been controversial and the reader is referred to the review of Inscho in this issue [81] for a comprehensive discussion. There is evidence for a role of ATP conversion to adenosine, which then leads to arteriolar contraction via adenosine A 1 receptors.…”

Ectonucleotidases in the kidney

“…In addition, NTPDase1 may specifically affect renal blood flow and glomerular filtration. Stimulation of P2X 1 receptors by ATP in afferent arterioles causes vasoconstriction (see article by Inscho [33] in this Special Issue); hydrolysis of locally produced ATP may therefore be important in maintaining renal blood flow. In this context, circulating or locally produced diadenosine polyphosphates can also cause vasoconstriction of afferent arterioles [34], and NPPs can hydrolyse these compounds.…”

“…As described elsewhere in this Special Issue (see articles by Inscho [33] and Bell et al [37]), there is evidence that ectonucleotidases play a pivotal role in tubuloglomerular feedback (TGF), whereby changes in renal perfusion pressure, or other causes of altered NaCl delivery to the macula densa, ultimately cause compensatory changes in afferent arteriolar resistance so that glomerular filtration rate is regulated [38]. ATP concentrations in renal interstitial fluid increase in response to elevations in renal arterial perfusion pressure [39], and, as indicated above, ATP can act directly on P2X 1 receptors on the afferent arteriole to …”