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Connexins and the Kidney

Connexins 37 and 40 transduce purinergic signals mediating renal autoregulation

Department of Nephrology, Saitama Medical College, Japan, and Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Australia

Submitted 19 April 2007 ; accepted in final form 8 October 2007

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 ^Cx37,43GAP27 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). The additional administration of 8-cyclopentyl- 1,3-dipropylxanthine (CPX) produced a further elevation of autoregulatory index of RPF (0.86 ± 0.07, P < 0.05) and GFR (0.88 ± 0.09, P < 0.05), compared with ^Cx37,43GAP27 alone. However, the addition of pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS) to ^Cx37,43GAP27 did not. Combined treatment with CPX and PPADS markedly worsened autoregulatory index of RPF (0.04 ± 0.10 to 0.81 ± 0.06, n = 6 P < 0.01) and GFR (0.05 ± 0.08 to 0.79 ± 0.05, P < 0.01). ^Cx40GAP27 induced similar changes to ^Cx37,43GAP27. Renal autoregulation was preserved in the presence of ^Cx43GAP26. Our results indicate that the inhibition of gap junction impaired renal autoregulation. Furthermore, the present data provide evidence that both adenosine and purinergic receptors contribute to glomerular autoregulation. Finally, our findings suggest that gap junctions, at least in part, transduce purinergic signals mediating renal autoregulation.

adenosine; adenosine 5'-triphosphate; renin-angiotensin system