TISSUE-SPECIFIC EXPRESSION OF HUMAN ANGIOTENSIN-II AT1 AND AT2 RECEPTORS AND CELLULAR-LOCALIZATION OF SUBTYPE MESSENGER-RNAS IN ADULT HUMANRENAL-CORTEX USING IN-SITU HYBRIDIZATION

All studies analyzing the localization of angiotensin II (Ang II) rece ptors in the human kidney have been performed at the protein level usi ng I-125-Ang II as a probe. In this study, cellular localizations of A ng II type I (AT1-R) and type 2 (AT2-R) receptor mRNAs in the adult hu man renal cortex were examined for the first time using in situ hybrid ization, and their expression patterns determined by RNase protection assay were compared with those in other human tissues. In the human re nal cortex obtained from tumor-free portions in renal cell carcinoma, AT1-R mRNA levels were about 8- to 10-fold higher than AT2-R mRNA leve ls. Human liver and aorta predominantly expressed AT1-R mRNA, while hu man right atrium contained both AT1-R and AT2-R mRNAs. Ligand-binding assays revealed that the total Ang II receptor number in the human ren al cortex was 16.0 +/- 3.3 fmol/mg protein, similar to that in liver ( 17.7 +/- 5.8) but significantly higher than in right atrium (11.6 +/- 3.2) and aorta (5.6 +/- 2.7). Relative distribution ratios of AT1-R an d AT2-R numbers in the renal cortex and right atrium were 82/17 and 56 /42%, respectively. In situ hybridization study indicated that stronge st AT1-R mRNA signals were located in interlobular arteries and tubulo interstitial fibrous regions surrounding interlobular arteries and glo meruli, followed in decreasing order by glomeruli and cortical tubules . Expression of AT2-R mRNA was highly localized in interlobular arteri es. Cells present in tubulointerstitial regions were positive for vime ntin and collagen type 1, indicating that the majority of the cells pr esent in the regions are fibroblasts. Presence of strong AT1l-R mRNA s ignals in the tubulointerstitial fibrous regions surrounding arteries and glomeruli and the expression of AT2-R mRNA in the interlobular art ery were the first evidence, suggesting a pharmacological framework fo r the differential effects of Ang II receptor subtype mediated renal f unction in the adult human kidney.