Connexins 37 and 40 transduce purinergic signals mediating renal autoregulation.

  title={Connexins 37 and 40 transduce purinergic signals mediating renal autoregulation.},
  author={Tsuneo Takenaka and Tsutomu Inoue and Yoshihiko Kanno and Hirokazu Okada and Caryl E. Hill and Hiromichi Suzuki},
  journal={American journal of physiology. Regulatory, integrative and comparative physiology},
  volume={294 1},
Our previous data indicated that various subtypes of connexin (Cx) were expressed in the juxtaglomerular apparatus. Experiments were performed to characterize the effects on renal autoregulation of specific mimetic peptides that inhibit these Cx subtypes in Wistar-Kyoto rats. Intrarenal infusion of (Cx37,43)GAP27 increased autoregulatory index of renal plasma flow (0.06 +/- 0.05 to 0.47 +/- 0.06, n = 6, P < 0.05) and glomerular filtration rate (GFR; 0.01 +/- 0.07 to 0.49 +/- 0.07, P < 0.05… 

Figures and Tables from this paper

Direct assessment of tubuloglomerular feedback responsiveness in connexin 40-deficient mice.

The TGF response magnitude in superficial cortical nephrons is reduced by 30-50% in mice without Cx40, but that with the exception of a small number of nephron, residual TGF activity is maintained, perhaps by determining the kinetics of signal transmission.

Elucidating mechanisms underlying altered renal autoregulation in diabetes.

The present data provide the first demonstration for a salt paradox in type 2 diabetes and implicate that in addition to Cx alterations, an enhanced proximal reabsorption attenuates TGF, underlying glomerular hyperfiltration and RAS activation.

Effect of ramipril on the regulation of the expression of connexins 40 and 43 in a rabbit model of arterial balloon injury.

The aim of this study was to determine whether Cx40 and Cx43 play different roles in the renin-angiotensin system (RAS) involved in the remodeling of GJs in VSMCs under pathological conditions.

ATP, P2 receptors and the renal microcirculation

  • E. Inscho
  • Biology, Medicine
    Purinergic Signalling
  • 2009
Findings related to the role of P2 receptors in regulating renal microvascular function and the respective roles of ATP and adenosine in autoregulatory resistance adjustments are consolidated and areas of controversy are presented.

Connexins and the Kidney Connexin 45 is expressed in the juxtaglomerular apparatus and is involved in the regulation of renin secretion and blood pressure

The localization of Cx45 to the JGA and functional data from C x45fl/fl:Nestin-Cre mice suggest that Cx 45 is involved in the propagation of JGA vascular signals and in the regulation of renin release and blood pressure.

Renal autoregulation in health and disease.

A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma.

Regulation of Renal Hemodyamics by Purinergic Receptors in Angiotensin II -Induced Hypertension

Both, P1 and P2 receptors participate in the in the regulation of vascular tone and hemodynamics in the kidney microvasculature, and have an important role in the tubuloglomerular feedback mechanism.

Altered gap junctional communication and renal haemodynamics in Zucker fatty rat model of type 2 diabetes

The findings indicate that ZDF rats have glomerular hyperfiltration with impaired autoregulation and an impairment of gap junctional communication in juxtaglomerular apparatus plays a role in altered renal autoreGulation in diabetes.

Contribution of renal purinergic receptors to renal vasoconstriction in angiotensin II-induced hypertensive rats.

There is an enhanced P2 receptor-mediated vasoconstriction of afferent and efferent arterioles in chronic Ang II-infused rats, which contributes to the increased renal vascular resistance observed in ANG II-dependent hypertension.



Exogenous 5'-nucleotidase improves glomerular autoregulation in Thy-1 nephritic rats.

The results indicate that renal autoregulation is impaired in Thy-1 nephritis and provide evidence that prostanoids contribute to maintain renal circulation in nephritic rats, and suggest that mesangial cells and/or 5'-nucleotidase plays an important role in mediating renal autOREgulation.

Effects of connexin-mimetic peptides on nitric oxide synthase- and cyclooxygenase-independent renal vasodilation.

Inhibition of gap junctional communication with connexin-mimetic peptides blocks EDHF-mediated signal transmission in vivo, as suggested by the abolishment of L-NAME- and indomethacin-resistant renal vasodilation.

Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade.

Results from anesthetized rats are consistent with the concept that activation of A1-receptors on vascular cells of the afferent arterioles participates in the mediation of TGF responses.

Connexins 40 and 43 are differentially regulated within the kidneys of rats with renovascular hypertension.

Cell-to-cell communication mediated by Cx40 may be implicated in the function of renin-secreting cells, hence participating in the control of blood pressure.

Attenuated renovascular constrictor responses to angiotensin II in adenosine 1 receptor knockout mice.

It is concluded that chronic A1AR deficiency diminishes the effectiveness of ANG II to constrict renal resistance vessels and to reduce GFR.

Paracrine factors in tubuloglomerular feedback: adenosine, ATP, and nitric oxide.

The application of the knockout technique has shown that adenosine 1 receptors are absolutely required for eliciting TGF responses, and there is also evidence that ATP may activate P2 receptors in preglomerular vessels, which may contribute to autoregulation of renal vascular resistance.

Physiological role for P2X1 receptors in renal microvascular autoregulatory behavior.

Data provide compelling new evidence indicating that tubuloglomerular feedback signals are coupled to autoregulatory preglomerular vasoconstriction through ATP-mediated activation of P2X1 receptors.

Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion

It is shown that in the absence of connexin40 (Cx40), which form gap junctions between juxtaglomerular and endothelial cells, the negative control of renin secretion and synthesis by angiotensin II and by intravasal pressure is abrogated, while the regulation by salt intake andrenergic stimulation is maintained.

Mediation of tubuloglomerular feedback by adenosine: Evidence from mice lacking adenosine 1 receptors

A1AR null mutant mice are a promising tool to study the functional role of A1AR in different target tissues and suggest that adenosine is a required constituent of the juxtaglomerular signaling pathway.

Differential connexin expression in preglomerular and postglomerular vasculature: accentuation during diabetes.

The renal vasculature and mesangial cells are well coupled on the preglomerular side but there is little evidence that the coupling extends into the efferent arteriole, and this pattern of cell coupling is accentuated during diabetes.