Evidence favoring the existence of two high molecular weight precursor forms of dog kidney renin.

ABSTRACT

Extraction of canine renal cortical tissue at pH 7.4 in the presence of the protease inhibitors diisopropylfluorophosphate (0.2 mM), Na2EDTA (7.8 mM), sodium tetrathionate (7.8 mM). N-ethyl maleimide (7.8 mM) yielded renin activity in two high molecular weight (HMW) forms, 65,000 (65K) and 55,000 (55K). Serial gel filtration chromatography of such extracts stored at 4 C showed that over the course of 2 days, activity at both 65,000 and 55,000 decreased almost entirely, while low molecular weight (LMW) activity at 41,000 (41K), not present immediately after extraction, had appeared in the extracts, The renin activity of the extract doubled over the first 24 h of storage and remained stable over the next 24 h. The activity of all three renin forms was comparably inhibited by antirenin antibodies. Our results support the concept that HMW renin(s) is a biological precursor of 41K renin. The new finding of a renin form intermediate in apparent molecular weight between 65K and 41K renin suggests that proteolytic processing of HMW to LMW renin may involve more than one step. The fact that in vitro conversion of HMW to LMW renin will occur under these conditions but takes place slowly may provide a technique for the future study of the precise manner in which HMW is converted to LMW renin.