Nicotinic acetylcholine receptor expression and regulation in the rat kidney after ischemia-reperfusion injury.
The cholinergic anti-inflammatory pathway is a mechanism whereby local inflammation is modulated by the brain via the vagus nerve and nicotinic acetylcholine receptors (nAChRs). The nAChR family are ligand-gated ion channels that consist of many different subtypes formed by the specific assembly of five polypeptide subunits including alpha1-10, beta1-4, gamma, delta, and epsilon. The alpha7 receptor (alpha7nAChR) mediates the anti-inflammatory effects of cholinergic stimulation. We recently demonstrated that cholinergic agonists attenuate renal ischemia-reperfusion (I/R) injury in rats. We also showed that tubular epithelial cells express functional nAChRs in vitro. The current studies report the expression, localization, and regulation of the alpha7nAChR in the rat kidney after I/R injury. We also examined, in this model, potential interactions between cholinergic stimulation and the STAT3 pathway, a key signaling cascade that has been linked to alpha7nAChR activation. RT-PCR and immunohistochemistry showed constitutive expression of many nAChR subunits. Immunohistochemistry localized basal alpha7nAChR expression to the endothelium of cortical peritubular capillaries, and its distribution was upregulated after I/R injury. Western blotting also showed an increase in alpha7nAChR subunit protein after renal I/R injury. Interestingly, pretreatment with nicotine, which improves the outcome after renal I/R injury, reduced the alpha7nAChR protein after I/R injury. Finally, we found that I/R injury stimulated the STAT3 pathway, whereas pretreatment with nicotine downregulated its activation. These results suggest that the alpha7nAChR plays an important role in the pathophysiology of renal I/R injury.
Yeboah
Michael M
MM
The Susan & Herman Merinoff Center for Patient Oriented Research, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA.
Xue
Xiangying
X
Javdan
Mohammad
M
Susin
Myron
M
Metz
Christine N
CN
D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018679:Cholinergic Agonists; C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D046988:Proteasome Endopeptidase Complex