Protein phosphatase 2A B56alpha during development in the spontaneously hypertensive rat.

Mistargeting of the regulatory subunit of protein phosphatase 2A (PP2A), B56alpha is involved in the hyperphosphorylation and desensitization of the D1 dopamine receptor in renal proximal tubules of spontaneously hypertensive rats (SHRs). However, the renal expression of B56alpha before hypertension develops is not known. Therefore, we studied the expression of B56alpha and PP2A activity in the kidney during development in the SHR and its normotensive control, the Wistar-Kyoto (WKY) rat. PP2A B56alpha was expressed in proximal and distal tubules with no differences in the pattern of expression in WKY and SHRs at any age. In brush border membranes of renal proximal tubules, PP2A B56alpha protein was greatest in the immature rats and decreased with development. However, PP2A activity did not change with age. PP2A B56alpha protein and PP2A activity were similar in WKY and SHRs except at 2 weeks when both PP2A B56alpha protein and PP2A activity were higher in SHRs than in WKY rats. The PP2A catalytic subunit co-immunoprecipitated with the D1 receptor in renal proximal tubule cells. It is possible that the increased expression of PP2A B56alpha and increased basal PP2A activity in the young, especially in the SHRs, may serve as a compensatory mechanism in the increased phosphorylation and decreased renal D1 receptor function, including D1-receptor mediated stimulation in renal proximal tubules of SHRs.