Research Article Expression of Acetylcholine Receptors by Experimental Rat Renal Allografts Marion Meixner, Srebrena Atanasova, Winfried Padberg, and Veronika Grau Laboratory of Experimental Surgery, Department of General and oracic Surgery, Justus-Liebig-University Giessen, Feulgenstraße 10-12, 35392 Giessen, Germany Correspondence should be addressed to Marion Meixner; marion.meixner@chiru.med.uni-giessen.de Received 9 April 2014; Accepted 6 June 2014; Published 9 July 2014 Academic Editor: Koichiro Kawashima Copyright © 2014 Marion Meixner et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chronic allograf injury (CAI) is a major cause for renal allograf dysfunction and characterized by vasculopathies, tubular atrophy, and fbrosis. We demonstrated that numerous leukocytes interact with vascular endothelial cells of allografs and produce acetylcholine, which contributes to vascular remodeling. Te cholinergic system might be a promising target for the development of novel therapies. However, neither the cellular mechanisms nor the acetylcholine receptors involved in CAI are known. Kidney transplantation was performed in the Lewis to Lewis and in the Fischer-334 to Lewis rat strain combination, which is an established experimental model for CAI. Expression of nicotinic and muscarinic acetylcholine receptors mRNA was quantifed in renal tissue by real-time RT-PCR on days 9 and 42 afer surgery. We detected CHRNA2–7, CHRNA10, CHRNB2, CHRNB4, and CHRM1– 3 mRNA in normal kidneys and in renal transplants. In contrast, CHRNA9, CHRM4, and CHRM5 mRNA remained below the threshold of detection. In renal allografs, CHRNA3 and CHRNB4 mRNA expression were dramatically reduced compared to isografs. In conclusion, we demonstrated that most acetylcholine receptor subtypes are expressed by normal and transplanted kidneys. Allograf rejection downmodulates CHRNA3 and CHRNB4 mRNA. Te role of diferent acetylcholine receptor subtypes in the development of CAI remains to be established. 1. Introduction Chronic allograf injury (CAI) is the most important cause of renal transplant failure in the long run, and up to now no efective therapies exist. CAI is associated with graf arterial intimal hyperplasia, glomerulopathy, interstitial fbrosis, and tubular atrophy [1]. Te pathogenesis of CAI is poorly understood, but acute rejection episodes are a major risk factor and seem to trigger graf remodeling. To gain insights into the pathogenesis of CAI, relevant experimental models are of utmost importance. Rat renal transplantation in the Fischer-344 (F344) to Lewis rat strain combination closely refects human CAI [2–6]. Of note, a severe acute rejection episode peaks around day 9 posttrans- plantation and spontaneously resolves [7–10]. Six months afer transplantation, however, renal function is impaired and all histopathological hallmarks of CAI are detected in allografs [8, 9]. Tis model opens up the possibility to investigate the contribution of acute rejection to CAI, which is difcult in patients. Using this experimental model, we observed numerous interactions of mononuclear intravascu- lar leukocytes with endothelial cells of capillaries, veins, and arteries during acute rejection, which seem to contribute to the pathogenesis of allograf vasculopathies [7, 9]. Tese mononuclear allograf leukocytes express in- creased levels of the high-afnity choline transporter 1 (CHT1), mediating the uptake of choline into the cell, as well as increased levels of the choline acetyltransferase (ChAT), responsible for the synthesis of acetylcholine (ACh) [8]. Accordingly, authentic ACh was detected in these mononu- clear leukocytes isolated from blood vessels of the grafs [8]. ACh receptor (CHR) activation plays a pivotal role in vascular remodeling [11–14] and in hyperproliferative disorders, which involve proliferation of fbroblasts and angiogenesis [15– 21]. Hence, we postulated that leukocytic ACh contributes to the pathogenesis of CAI. As a proof of concept, we treated allograf recipients with the dual-specifc choline esterase inhibitor rivastigmine, which should increase levels Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 289656, 9 pages http://dx.doi.org/10.1155/2014/289656