Connexins 37 and 40 transduce purinergic signals mediating renal autoregulation.
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). 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 (Cx37,43)GAP27 alone. However, the addition of pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS) to (Cx37,43)GAP27 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). (Cx40)GAP27 induced similar changes to (Cx37,43)GAP27. Renal autoregulation was preserved in the presence of (Cx43)GAP26. 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.
Takenaka
Tsuneo
T
Department of Nephrology, Saitama Medical College, Iruma Saitama, Japan.
Inoue
Tsutomu
T
Kanno
Yoshihiko
Y
Okada
Hirokazu
H
Hill
Caryl E
CE
Suzuki
Hiromichi
H
D000818:Animals; D017630:Connexins / Q000494:pharmacology / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology*; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D008297:Male; D009842:Oligopeptides; D010455:Peptides / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D011983:Receptors, Purinergic / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D017630:Connexins; D005665:Furosemide; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D011732:Pyridoxal Phosphate; D011983:Receptors, Purinergic; D018047:Receptors, Purinergic P1; D049994:Sodium Potassium Chloride Symporter Inhibitors; D014970:Xanthines; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C514423:Gap 26 peptide; C455880:gap 27 peptide; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C051360:1,3-dipropyl-8-cyclopentylxanthine