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- Title
Functional Expression of Key Components of the Olfactory Receptor Signaling Pathway in the Distal Nephron.
- Authors
Pluznick, Jennifer L.; Xiaohong Zhang; Dong-Jing Zou; Qingshang Yan; Wells, Erika; Tong Wang; Firestein, Stuart; Caplan, Michael J.
- Abstract
Recent studies have shown that olfactory receptors (ORs) are functionally expressed in non-olfactory tissues. A potential role for ORs in the kidney, however, has yet to be investigated. We find that key components of the OR signaling pathway, olfactory G protein (Golf) and the olfactory-related adenylyl cyclase (AC3), are detectable in the kidney by RT-PCR as well as by western blot. AC3 and Golf are distinctly expressed in a subset of tubule segments where they colocalize with one another, as well as with markers of the distal convoluted tubule (NaCl cotransporter and calbindin). We have also observed AC3 staining in macula densa (MD) cells. MD cells are known to be important controllers of glomerular filtration rate (GFR). Renal function studies using AC3-/- mice and wild-type littermates demonstrated that renal function in ACT-/- mice, as measured by GFR, is significantly decreased (0.42 ± 0.08 ml/min/100g BW, n=8 in ACT-/- vs. 0.87 ± 0.06, n=6 for AC3-/-; p<0.01). In order to identify which, if any, OR's are expressed in kidney we made use of a custom designed Affymetrics microarray in which the entire family of mouse OR genes (>1000) is represented. RNA was prepared from three normal mouse kidneys and the array was screened according to standard methods. We found that mouse kidney expresses approximately 80 ORs. These studies indicate that the machinery necessary for olfactory-like signaling is present in the kidney. Intriguingly, this machinery is found in the MD/distal tubule, ideal localizations for ORs to serve as sensors of the chemical composition of the forming urine and regulators of GFR.
- Subjects
SENSORY receptors; OLFACTORY nerve; KIDNEY tubules; G proteins; ADENYLATE cyclase; GLOMERULAR filtration rate; KIDNEY function tests; LABORATORY mice
- Publication
FASEB Journal, 2007, Vol 21, Issue 5, pA500
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.5.a500