Lectin chromatography of extrarenal renin protein in human plasma and tissues: Potential endocrine function via the renin receptor

Stubbs, Anthony J.; Skinner, Sandford L.

doi:10.3317/jraas.2004.039

Cited by 8 publications

(4 citation statements)

References 34 publications

(62 reference statements)

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“…Finally, renin inhibitors may provide additional protection over other RAS inhibitors, by interfering with the enhanced catalytic activity of renin and prorenin after the binding of these molecules to the (pro)renin receptor 48 . In addition, if renin inhibitors not only block the enzymatic activity of renin in vivo , but also change the conformation of prorenin both in vitro 49 and in vivo , 50 then they may also modify renin metabolism 51 and binding to various receptors, including the (pro)renin receptor 48 or the MP6 receptor 52,53 . These specific characteristics of renin inhibitors may be potentially useful in patients with diabetes mellitus in whom prorenin levels are a powerful predictor of microvascular complications 54,55 or if prorenin has a direct toxic effect 56 …”

Section: Biochemical Differences Between Renin Inhibitors and Other Rmentioning

confidence: 99%

Renin Inhibition With Aliskiren

Wuerzner

Azizi²

2008

Clin Exp Pharma Physio

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1. Initial attempts to inhibit renin in humans have faced numerous difficulties. Molecular modelling and X-ray crystallography of the active site of renin have led to the development of new orally active renin inhibitors, such as aliskiren. 2. Aliskiren has a low bioavailability (between 2.6 and 5.0%) compensated by its high potency to inhibit renin (IC50: 0.6 nmol/L) and a long plasma half-life (23-36 h), which makes it suitable for once-daily dosing. 3. The once-daily administration of aliskiren to hypertensive patients lowers BP as strongly as standard doses of established angiotensin II type 1 (AT1) receptor blockers (losartan, valsartan, irbesartan), hydrochlorothiazide, angiotensin converting enzyme inhibitors (ramipril and lisinopril) or long acting calcium channel blockers (amlodipine). In combination therapy, aliskiren further decreases blood pressure when combined with either hydrochlorothiazide, amlodipine, irbesartan or ramipril. 4. The biochemical consequences of renin inhibition differ from those of angiotensin I-converting enzyme (ACE) inhibition and Ang II antagonism, particularly in terms of angiotensin profiles and interactions with the bradykinin-nitric oxide-cyclic guanosine monophosphate pathway and possibly the (pro)renin receptor. 5. Blockade of the renin angiotensin system (RAS) with ACE inhibitors, AT1 receptor blockers or a combination of these drugs has become one of the most successful therapeutic approaches in medicine. However, it remains unclear how to optimize RAS blockade to maximize cardiovascular and renal benefits. In this context, renin inhibition to render the RAS fully quiescent is a new possibility requiring further study.

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Section: Biochemical Differences Between Renin Inhibitors and Other Rmentioning

confidence: 99%

Renin Inhibition With Aliskiren

Wuerzner

Azizi²

2008

Clin Exp Pharma Physio

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“…The first step of the RAS involves the cleavage of angiotensinogen into angiotensin (Ang) I (1-10) by renin, which is an aspartyl protease (EC 3.4.23.15) that belongs to the protein family peptidase A1. So far, an active renin is known to originate in the juxtaglomerular cells of the kidneys, although extrarenal sources of (pro)renin are known [82,83]. Further on, a decapeptide Ang I is converted into either an octapeptide Ang II (1-8) by the angiotensin-converting enzyme (ACE; EC 3.4.17.23), a nanopeptide Ang (1-9) by the angiotensin-converting enzyme 2 (ACE2; EC 3.4.17.23), or a heptapeptide Ang (1-7) by neprylysin (a neural endopeptidase; EC 3.4.24.11).…”

Section: What Are the Key Components Of The Renin-angiotensin System ...mentioning

confidence: 99%

Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin–Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions

Khan,

Kurnik-Łucka,

Latacz

et al. 2024

IJMS

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In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin–angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin–angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both renin–angiotensin and dopaminergic systems influence intestinal Na+/K+-ATPase activity, thus maintaining electrolyte and nutritional homeostasis. The colocalization of B0AT1 and ACE2 indicates the direct role of the renin–angiotensin system in amino acid absorption. Yet, more studies are needed to thoroughly define the structural and functional interaction between TJ-associated proteins and GI renin–angiotensin and dopaminergic systems.

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“…In addition, if renin inhibitors not only block the enzymatic activity of renin in vivo, but also change the conformation of prorenin both in vitro [58] and in vivo [59 ], then they may also modify renin metabolism [60] and binding to its receptors, including the (pro)renin receptor [53] or the MP6 receptor [52,54 ]. These specific characteristics of renin inhibitors may be potentially useful in patients with diabetes mellitus in whom prorenin levels are a powerful predictor of microvascular complications [61,62], or if prorenin has a direct toxic effect [63].…”

Section: Biochemical Differences Between Renin Inhibitors and Other Smentioning

confidence: 99%

Renin inhibition

Azizi

2006

Current Opinion in Nephrology &Amp; Hypertension

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Blockade of the renin-angiotensin system with angiotensin I-converting enzyme inhibitors, angiotensin II type 1 receptor blockers or a combination of these drugs has become one of the most successful therapeutic approaches in medicine. It remains unclear, however, as to how to optimize the renin-angiotensin system blockade to maximize cardiovascular and renal benefits. In this context, renin inhibition to render the renin-angiotensin system fully quiescent is a new possibility requiring further study.

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Lectin chromatography of extrarenal renin protein in human plasma and tissues: Potential endocrine function via the renin receptor

Abstract: Secretion of prorenin from extrarenal tissues comprises approximately half of the renin protein in plasma; its origin is unknown.

Cited by 8 publications

References 34 publications

Renin Inhibition With Aliskiren

Renin Inhibition With Aliskiren

Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin–Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions

Renin inhibition

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