title: Expression of acetylcholine receptors by experimental rat renal allografts.
abstract: Chronic allograft injury (CAI) is a major cause for renal allograft dysfunction and characterized by vasculopathies, tubular atrophy, and fibrosis. We demonstrated that numerous leukocytes interact with vascular endothelial cells of allografts and produce acetylcholine, which contributes to vascular remodeling. The 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 quantified in renal tissue by real-time RT-PCR on days 9 and 42 after 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 allografts, CHRNA3 and CHRNB4 mRNA expression were dramatically reduced compared to isografts. In conclusion, we demonstrated that most acetylcholine receptor subtypes are expressed by normal and transplanted kidneys. Allograft rejection downmodulates CHRNA3 and CHRNB4 mRNA. The role of different acetylcholine receptor subtypes in the development of CAI remains to be established.
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Feulgenstraße 10-12, 35392 Giessen, Germany.
authors.forename: Marion
authors.identifier: 0000-0002-6882-5426
authors.initials: M
authors.lastname: Meixner
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Feulgenstraße 10-12, 35392 Giessen, Germany.
authors.forename: Srebrena
authors.initials: S
authors.lastname: Atanasova
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Feulgenstraße 10-12, 35392 Giessen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Padberg
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Feulgenstraße 10-12, 35392 Giessen, Germany.
authors.forename: Veronika
authors.identifier: 0000-0001-7512-2051
authors.initials: V
authors.lastname: Grau
mesh_terms: D064591:Allografts / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011950:Receptors, Cholinergic