RT Journal Article
SR Electronic
T1 RETRACTION: Mechanisms Underlying the Renoprotective Effect of GABA against Ischemia/Reperfusion-Induced Renal Injury in Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 767
OP 774
DO 10.1124/jpet.111.180174
VO 338
IS 3
A1 Shuhei Kobuchi
A1 Ryosuke Tanaka
A1 Takuya Shintani
A1 Rie Suzuki
A1 Hidenobu Tsutsui
A1 Mamoru Ohkita
A1 Kazuhide Ayajiki
A1 Yasuo Matsumura
YR 2011
UL http://jpet.aspetjournals.org/content/338/3/767.abstract
AB The excitation of the renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury (AKI) in rats. We have reported that intravenous treatment with GABA has preventive effects on ischemia/reperfusion (I/R)-induced renal dysfunction with histological damage in rats. However, detailed mechanisms of the action of GABA on the renal injury were still unknown. Therefore, in the present study, we aimed to clarify the detailed mechanisms of GABA in ischemic AKI in rats. Ischemic AKI was induced by clamping the left renal artery and vein for 45 min. Thereafter, the kidney was reperfused to produce I/R-induced injury. Intravenous or intracerebroventricular treatment with 3-[[[(3,4-dichlorophenyl)methyl]amino]propyl] diethoxymethyl) phosphinic acid (CGP52432), a GABAB receptor antagonist, abolished the suppressive effects of intravenously applied GABA on enhanced renal sympathetic nerve activity during ischemia, leading to the elimination of the renoprotective effects of GABA. Intracerebroventricular treatment with GABA or intravenous treatment with baclofen, a selective GABAB receptor agonist, prevented I/R-induced renal injury equivalent to intravenous treatment with GABA. However, intravenous treatment with bicuculline, a GABAA receptor antagonist, failed to affect the preventive effects of GABA on ischemic AKI. Therefore, we demonstrated the novel finding that the preventive effect of GABA on ischemic AKI through the suppression of enhanced renal sympathetic nerve activity induced by renal ischemia is presumably mediated via GABAB receptor stimulation in the central nervous system rather than peripheral GABAB receptor.