TY - JOUR
T1 - Connexins 37 and 40 transduce purinergic signals mediating renal autoregulation
AU - Takenaka, Tsuneo
AU - Inoue, Tsutomu
AU - Kanno, Yoshihiko
AU - Okada, Hirokazu
AU - Hill, Caryl E.
AU - Suzuki, Hiromichi
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Adenosine
KW - Adenosine 5′-triphosphate
KW - Renin-angiotensin system
UR - http://www.scopus.com/inward/record.url?scp=38149083964&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00269.2007
DO - 10.1152/ajpregu.00269.2007
M3 - Article
SN - 0363-6119
VL - 294
SP - R1-R11
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 1
ER -