Published Online
on July 14, 2003

A more recent version of this article appeared on August 1, 2003

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Submitted on April 9, 2003
Revised on May 1, 2003

Intracellular Renin and the Nature of Intracrine Enzymes

Richard N. Re^*

From the Research Division, Ochsner Clinic Foundation, New Orleans, La.

^* To whom correspondence should be addressed. E-mail: rre{at}ochsner.org.

Abstract--Recently, the binding of renin and prorenin to cellular receptors with the subsequent generation of second messengers and the production of physiological effects has been demonstrated. In addition, the internalization of prorenin by target cells has been associated with increased cellular synthesis of angiotensin and cardiac pathology. Also, a renin transcript lacking the sequences encoding a secretory signal has been reported, and this transcript appears to produce a renin that acts in the cell that synthesized it. Some years ago, we coined the term intracrine for a peptide hormone or factor that acts in the intracellular space either after internalization or retention in its cell of synthesis. Thus defined, a wide variety of peptides display intracrine functionality, including hormones, growth factors, transcription factors, and enzymes. For example, considerable evidence indicates that angiotensin II is an intracrine. Also, general principles of intracrine functionality have been developed. Thus, recent evidence demonstrates that the prorenin/renin molecule is an intracrine enzyme. Here, the actions of intracrine enzymes (angiogenin, phosphoglucose isomerase, phospholipase A2, granzyme A and B, thioredoxin, platelet-derived endothelial growth factor, and serine protease inhibitors) are reviewed. The relation of prorenin/renin to other intracrine enzymes, and to intracrines in general, is discussed.

Key words: renin • platelet-derived growth factor • enzymes • angiotensin II • phospholipases

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