Key result
Cloned murine AT2 receptors match peak III receptors, suggesting a novel AT2 subtype remains uncloned.
Why the study?
N1E-115 cells possess two distinct subpopulations of AT2 receptors with different pharmacological, biochemical, and immunological properties, but only one receptor type had been cloned.
The study provides evidence for AT2 receptor heterogeneity by demonstrating that the cloned AT2 receptor from murine neuroblastoma cells corresponds to the peak III subpopulation.
AT2 receptor heterogeneity may exist in neuronal cells; leaves open cloning of peak I and human validation.
Homology-based PCR was used to isolate angiotensin II type 2 (AT2) receptor cDNA from murine neuroblastoma N1E-115 cells. Despite subtle differences in the nucleotide sequence (the N1E-115 clone coded for Phe133 as TTC and Gln326 as CAG; base substitutions are in bold-italics), the AT2 receptor protein was identical to other reported murine AT2 clones. When transfected into COS-1 cells, the expressed AT2 receptor displayed high affinity for AngII and for AT2-selective compounds, GTP gamma S-insensitive agonist binding and enhanced agonist binding by dithiothreitol. Previously, we have demonstrated that N1E-115 cells possess two distinct subpopulations of AT2 receptors, defined as peak I and peak III receptors, that can be separated by heparin-sepharose chromatography. The two subpopulations differ pharmacologically, biochemically and immunologically. The binding properties of the cloned AT2 receptor closely resembled that of peak III receptors. Moreover, antisera raised against peak I AT2 receptors failed to immunoreact to either peak III receptors or cloned AT2 receptors expressed in COS-1 cells. Collectively, these data suggest that the cloned AT2 receptor is identical to peak III receptors from N1E-115 cells and that a novel AT2 receptor (peak I) remains to be cloned.
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Yee et al. (1997) studied this question. Cloning and expression of AT2 receptor cDNA was evaluated on AT2 receptor characteristics and binding properties. The cloned AT2 receptor from murine neuroblastoma N1E-115 cells was identical to peak III receptors, suggesting a novel AT2 receptor (peak I) remains to be cloned.
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