Developmental expression patterns for angiotensin receptors in mouse skin and brain

Abstract

Two G-protein-coupled receptors, angiotensin type 1 receptor (AT1R) and type 2 receptor (AT2R), mediate the majority of angiotensin II (Ang II) effects. It has long been believed that the AT2R is reduced to extremely low levels in adulthood but is abundantly expressed in the fetus. However, recent data from rats and mice do not support this notion. Employing Western blot analysis, we found a gradual increase in AT2R protein expression from fetal life to adulthood in brain, heart, lung, liver, and kidney. The reason for the discrepancy between our observations and the conventional concept is unknown. Evidence supporting a regression of the AT2R during maturation is derived largely from autoradiographic signals that were confined to the outline of fetal rats, implying that the previously reported high AT2R expression in the fetus might be valid only for skin. We therefore hypothesized that the ontogeny of angiotensin receptors in skin is opposite that in other organs. In the current experiment, we employed Western blot analysis to compare AT2R and AT1R protein expressions in skin with that in the brainstem of fetal and adult mice. Fetal brainstem expressed lower AT2R and higher AT1R protein compared to adult brainstem (AT2R/GAPDH: 0.08 ± 0.2 in fetus vs 7.6 ± 0.9 in adult, p < 0.05; AT1R/GAPDH: 5.9 ± 0.8 in fetus vs 0.7 ± 0.3 in adult, p < 0.05). In contrast, fetal skin expresses higher AT2R and lower AT1R protein compared to adult skin (AT2R/GAPDH: 0.95 ± 0.4 in fetus vs 0.04 ± 0.2 in adult, p < 0.05; AT1R/ GAPDH: 0.6 ± 0.2 in fetus vs 2.1 ± 0.5 in adult, p < 0.05). This expression profile was also confirmed by immunofluorescence. Using real-time RT-PCR, we could not detect any significant differences in mRNA of these two receptors in brainstem between fetal and adult mice. However, we found a higher AT2R mRNA and lower AT1R mRNA in the fetal skin compared to adult skin. The above results confirm our hypothesis that skin displays an expression profile of angiotensin receptors opposite that of other organs during development, suggesting that the currently held view concerning AT2R maturation is suitable only for skin. In other organs and tissues, adults express higher AT2R protein than does the fetus.

Angiotensin type 2 receptor in pancreatic islets of adult rats: a novel insulinotropic mediator

“…1D1) 1D2) of developing rats from 1 day to 6 wk of age. This expression pattern is similar to that reported previously in the mouse brain stem (15,42). Interestingly, in the pancreas (Fig.…”

“…documented that this dogma may not be true (42). We found that adult rat (43) and mouse (15) expressed significantly higher AT 2 R protein compared with the fetus and neonate.…”

“…A series of experiments from our laboratory have demonstrated a higher AT 2 R expression in the adult rat and mouse compared with the fetus and neonate (15,42,43). These results imply a potential functional significance of this ANG II receptor subtype in mature animals, contrary to the concept that currently prevails (5,13).…”

“…1A3). Because AT 2 R protein has been demonstrated to be stably expressed in brain stem in our previous studies (15,42,43), the brain stem therefore was used to normalize AT 2 R expression in other tissues to obtain comparable expression levels. From Fig.…”

A Small Molecule Angiotensin II Type 2 Receptor (AT2R) Antagonist Produces Analgesia in a Rat Model of Neuropathic Pain by Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) and p44/p42 MAPK Activation in the Dorsal Root Ganglia

“…The AT 2 R is expressed in the brain and viscera of adult mice and on small‐ to medium‐sized DRG neurons in the adult rat and humans . In human tissue sections, the AT 2 R is expressed on nerve fibers in peripheral nerves, skin, urinary bladder, and bowel .…”