Extraction of Plasma Prorenin by Human Heart

Skinner, Sandford L.; Thatcher, R. L.; Whitworth, J. A.; Horowitz, J. D.

doi:10.1016/s0140-6736(86)91270-5

Cited by 26 publications

(5 citation statements)

References 20 publications

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“…However, the extent to which they process prorenin is not resolved. For example, prorenin has been reported to be extracted by the rodent vascular wall and human 79 and might be activated in these tissues for local Ang II generation. In primates, the liver and kidney take up circulating prorenin and convert it to renin without secreting renin back into the circulation.…”

Section: Cleavage Of the Prosegmentmentioning

confidence: 99%

Human prorenin.

1991

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Human prorenin is the enzymatically inactive biosynthetic precursor of renin. Recent interest has focused on the posttranslational sorting and processing of prorenin to renin since markedly increased levels of circulating prorenin have been associated with both physiological and pathological changes. These observations raise the question of whether prorenin processing may be a regulatory event in renin production in the kidney. In the juxtaglomerular cells of the kidney, prorenin can be sorted to either of two pathways: 1) the regulated pathway, which is mediated by secretory granules, where a thiol protease resembling cathepsin B processes prorenin to renin by cleavage of the amino terminal 43-amino acid prosegment, which allows exposure of the active site of renin, or 2) the constitutive pathway, which is not regulated and does not involve conversion of prorenin to renin. Studies in which segments of prorenin are modified by site-directed mutagenesis suggest that the prosegment and glycosylation are not required for sorting, although they may influence or participate in sorting, or both. Certain areas in the prosegment are important determinants of enzyme activity and ability to cleave the prosegment. Further structural analysis of prorenin will be useful to assess details of its sorting and processing. In addition, a number of extrarenal tissues such as uterine lining, ovarian theca, corpus luteum, pituitary, and adrenal, express the renin gene. These tissues have different capabilities to sort and process prorenin compared with kidney, and some tissues secrete only prorenin. Whether prorenin-to-renin conversion is necessary to activate these local renin-angiotensin systems is a key issue. Understanding mechanisms involved in prorenin-torenin conversion will help to dissect the potential regulatory role of this step in renin secretion, to define the physiological importance of extrarenal prorenin and renin production, and to determine whether the prorenin processing step could be a site for therapeutic intervention. (Hypertension 1991;17:469-479)

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Section: Cleavage Of the Prosegmentmentioning

confidence: 99%

Human prorenin.

1991

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“…In response to raised circulating concentrations of angiotensinogen, prorenin, and activated renin secreted from the liver and kidneys, respectively, ACE inhibited endothelial cells might begin sequestering and metabolising these extra circulating components. Although specific cell surface receptors mediating uptake of angiotensinogen and renin have not been identified, alterations in their post-translational glycosylation states known to occur during ACE inhibition might affect their interaction with the endothelial cell surface and their metabolism in some organs.24 25 A localised tissue specific contribution to vascular angiotensin production by initiation of de novo synthesis of ACE, angiotensinogen, and renin within certain endothelial cells as a result of activation of gene transcription remains a distinct possibility26-28 (despite considerable difficulties associated with its in vivo and in vitro analysis29 30), provided that there is efficient translation of the messenger RNA (mRNA) and secretion of the correctly processed mature proteins.3' Does induction of endothelial gene expression result in resistance to ACE inhibition in certain patients?…”

Section: Endothelial Functionmentioning

confidence: 99%

Diverse factors influencing angiotensin metabolism during ACE inhibition: insights from molecular biology and genetic studies

Morgan¹

1994

Heart

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“…Some have proposed that prorenin may have a direct action. 38 Although such an action would not preclude the traditional mechanisms already described, the validation of such actions in the ovary awaits direct data.…”

Section: Mechanism Of Ovarian Renin-angiotensin Systemmentioning

confidence: 99%