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(Hypertension. 2005;46:1069.)
© 2005 American Heart Association, Inc.

Brief Reviews

Renin, Prorenin and the Putative (Pro)renin Receptor

From the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam; and the Department of Internal Medicine (J.D.), UMCN St. Radboud, Nijmegen, The Netherlands

Correspondence to A.H.J. Danser, Department of Pharmacology, Room EE1418b, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail a.danser@erasmusmc.nl

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Renin is an aspartic protease that consists of 2 homologous lobes. The cleft in between contains the active site with 2 catalytic aspartic residues.¹ Unlike other aspartic proteases such as pepsin or cathepsin D, renin is monospecific and only cleaves angiotensinogen, to generate angiotensin (Ang) I. Ang I is the precursor of the active end-product of the renin-angiotensin system (RAS), Ang II.

Renin has also been called active renin to underline that an enzymatically inactive form of renin exists. In 1971, Lumbers found that amniotic fluid, left at low pH in the cold, acquired renin activity.² Later, Skinner described a similar phenomenon in plasma.³ Acidification was not strictly necessary for this increase in Ang I-generating activity, because incubation at low temperature also increased renin activity, albeit to only 15% of activity after acidification. Soon it was postulated that this inactive, but activatable "big" renin (its molecular weight was 5 kDa higher than that of renin) was the biosynthetic precursor of renin. Hence, it was named prorenin. Only with the cloning of the renin gene in 1984 was prorenin definitively proved to be the precursor of renin.⁴ For reasons that are unknown, prorenin circulates in human plasma in excess to renin, sometimes at concentrations that are 100-times higher.⁵ Prorenin has also been demonstrated in plasma of cat, dog, cattle, pig, horse, sheep, rabbit, rat, and mouse.

A 43-amino acid N-terminal propeptide explains the absence of enzymatic activity of prorenin. This propeptide covers the enzymatic cleft and obstructs access of angiotensinogen to . . . [Full Text of this Article]

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