Tissue-Specific Regulation of Renin-Binding Protein Gene Expression in Rats1

Abstract

Rat gene for renin-binding protein (RnBP) was shown to be expressed in the kidney, adrenal gland, brain, lung, spleen, ovary, testis, and heart. On sodium depletion and captopril administration, the rat showed a marked increase in the adrenal RnBP mRNA level and a slight decrease in the kidney RnBP mRNA level. In two-kidney, one clip hypertensive rats, the RnBP mRNA levels of the clipped and contralateral kidneys were unchanged and also its adrenal mRNA level was maintained at the control level. The recombinant rat RnBP was synthesized in Escherichia coli cells and purified to apparent homogeneity. The RnBP existed as a homodimer and formed a heterodimer with rat renin to inhibit renin activity extensively. Intravenous injection of the RnBP into rats resulted in a rapid and strong inhibition of plasma renin activity, which persisted at least for 2 h. These results suggest that the expression of RnBP gene in the kidney and adrenal gland is regulated independently, and the function of RnBP is related to electrolyte homeostasis, probably through the interaction with renin.

Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis.

“…43 A renin-binding protein has been described in various organs, including the heart. 44 Recently, it was proposed that prorenin becomes catalytically active after binding to a cell receptor. 45 Receptor binding of prorenin would unfold its prosegment, and this renders the active site accessible to angiotensinogen.…”

Biochemical, Structural and Pathophysiological Aspects of Prorenin and (Pro)renin Receptor

“…However, such binding and internalization could not generate any angiotensin peptides intracellularly. Besides, existence of renin/prorenin receptor independent of mannose 6-phosphate such as renin binding protein (RnBP), renin/prorenin binding protein (ProBP) in rat tissues, vascular renin binding protein have also been confirmed (Takahashi et al, 1983;Tada et al, 1992;Campbell et al, 1994;Sealy et al, 1996) that bind with different binding affinities to their ligands. Fig.…”

Amino acid residues conferring the nucleotide binding properties of N-acetyl-D-glucosamine 2-epimerase (renin binding protein)

“…The amino acid sequences were highly similar to each other and were characterized by the presence of a conserved leucine zipper motif (3,13). The expression of rat RnBP was detected mainly in the kidney, considerably in the adrenal gland, brain, lung, spleen, and ovary and slightly in the testes and heart by RNase protection analysis (10). Co-expression of human renin and RnBP cDNA in mouse AtT-20 cells showed that RnBP regulates active renin secretion from the transformant (5).…”