Potential effects of renin activation on the regulation of renin production.
In normal humans nearly half the renin in plasma and kidney is inactive. Human inactive renin can be activated by a variety of proteases and by exposure to low pH and is a putative biosynthetic precursor of renin, i.e., prorenin. Pulse-labeling studies in a human renin-secreting tumor suggest that renin is synthesized as a prepro- and proform, both of which are inactive. Using the cDNA probe to deduce the amino acid sequence of precursor renin from the nucleotide sequence of human kidney mRNA, the prosegment was estimated to be 46 amino acids long, similar to differences in molecular weight between active and inactive renin. In plasma of diabetic patients with nephropathy and the syndrome of hyporeninemic hypoaldosteronism, inactive renin levels are increased 3-5 times normal. The inability to activate renin in this syndrome strongly implies that conversion of inactive (pro-) renin to active renin may be physiologically relevant to active renin production. Furthermore, in normal humans profound stimulation of active renin can be accompanied by a reciprocal drop in circulating inactive renin levels. The beta-adrenergic system and prostaglandins are two major, but independent, mechanisms of stimulating renin release. Studies in our laboratory suggest that prostaglandins and the beta-adrenergic system may act at different sites in renin production: beta-stimulation may act at early steps in renin biosynthesis, while prostaglandins may act preferentially at later steps that possibly involve conversion of inactive to active renin. Proof of this hypothesis lies in purification of inactive renin to determine whether it is prorenin and in the use of the renin cDNA probe to study pre- vs. posttranslational events in renin processing.(ABSTRACT TRUNCATED AT 250 WORDS)
D000653:Amniotic Fluid / Q000201:enzymology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D002823:Chorion / Q000201:enzymology; D004274:DNA, Recombinant / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000502:physiology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007610:Kallikreins / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects; D008954:Models, Biological; D008970:Molecular Weight; D009392:Nephrectomy; D011247:Pregnancy; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000378:metabolism; D012083:Renin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D013363:Submandibular Gland / Q000378:metabolism
D004274:DNA, Recombinant; D004792:Enzyme Precursors; D011943:Receptors, Adrenergic, beta; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D000804:Angiotensin II; D002216:Captopril; D007610:Kallikreins; D012083:Renin; D002118:Calcium