Les récepteurs de l'angiotensine II dans le placenta humain sont de type AT<sub>1</sub>

Kalenga, M K; Gasparo, Marc de; Hertogh, R. De; Whitebread, Steven; Vankrieken, L.; Thomas, Karl

doi:10.1051/rnd:19910307

Cited by 35 publications

(10 citation statements)

References 17 publications

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“…In the rat foetus, the predominant All receptor subtype in a variety of tissues is the AT2 receptor although AT, mRNA is exclusively expressed in the major foetal blood vessels (Tsutsumi et al, 1991;Shanmugam et al, 1994). AT1 receptors have also been located in foetal blood vessels in the human placenta (Kalenga et al, 1991) (Stevenson & Lumbers, 1994) and suppresses the foetal pressor response to exogenous All (Stevenson et al, 1995) (Rankin & Phernetton, 1978) blood pressure responses to direct antagonism of the foetal RAS using saralasin, a non-specific All receptor antagonist, which suggests that the level of activity of the foetal RAS before treatment may be critical in determining the observed response.…”

Section: Discussionmentioning

confidence: 99%

Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Forhead

Whybrew

Hughes

et al. 1996

British J Pharmacology

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1 The effects of antagonism of the maternal renin-angiotensin system (RAS) with either an angiotensin II type 1-(ATI) specific receptor blocker (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) 9 The present study demonstrated that administration of either GR138950 or captopril to pregnant ewes effectively blocked the maternal RAS, and caused hypotension and a decrease in uterine blood flow. However, only captopril appeared to cross the placenta to influence directly the RAS of the sheep foetus. This suggests that the fall in foetal oxygenation observed after AT,-specific receptor blockade and ACE inhibition originates primarily from changes in the maternal and/or placental vasculature. Despite these changes, neither GR138950 nor captopril were detrimental to the outcome of pregnancy when foetal blood loss was kept to a minimum.

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Section: Discussionmentioning

confidence: 99%

Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Forhead

Whybrew

Hughes

et al. 1996

British J Pharmacology

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“…In addition, AT1R mRNA and AT1R protein levels are rising throughout the entire pregnancy, reaching highest levels at the end (61). Since a direct connection between Angiotensin II and AT1R has been observed in the placenta, it has been supposed that this fact indicates a regulating effect of Angiotensin II on the AT1R expression (62). From a more clinical point of view, there are several references that the placental RAS is involved in trophoblast invasion and angiogenesis (63, 64), being a possible cause of defect for the development of conditions with disordered utero-placental perfusion, namely preeclampsia (see below).…”

Section: Physiological Role Of the Ras In The Reproductive Tractmentioning

confidence: 99%

Local Renin-Angiotensin System in the Reproductive System

Herr

Bekes²,

Wulff³

2013

Front. Endocrinol.

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The renin-angiotensin system (RAS) is well known as regulator of electrolytes and blood pressure. Besides this function, there are numerous studies supporting the idea of a local tissue RAS. This system controls the local activity of the different RAS family members, especially of the functional proteins Angiotensin II and Angiotensin (1–7). Those antagonistically acting proteins have been described to be expressed in different organ systems including the human reproductive tract. Therefore, this local RAS has been suspected to be involved in the control and regulation of physiological and pathological conditions in the female reproduction tract. This review of the available literature summarizes the physiological influence of the RAS on the follicular development, ovarian angiogenesis, and placental- and uterine function. In addition, in the second part the role of the RAS concerning ovarian- and endometrial cancer becomes elucidated. This section includes possible novel therapeutic strategies via inhibition of RAS-mediated tumor growth and angiogenesis. Looking at a very complex system of agonistic and antagonistic tissue factors, it may be supposed that the RAS in the female reproduction tract will be of rising scientific interest in the upcoming years.

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“…Finally, MK-des-Arg has a very low affinity for the human B 1 R in a [ 3 H]Lys-des-Arg 9 -BK binding displacement assay (Charest-Morin & Marceau, 2016), suggesting that MK cannot be converted into an effective B 1 R agonist via reaction with hypothetical carboxypeptidases, including ACE2. Any effect of MK on AT 1 receptor for angiotensin, represented in the human umbilical vein and mediating a contractile response to angiotensin II (Altura et al, 1972; Kalenga et al, 1991), is ruled out by the inhibition of MK-induced contractile effects by icatibant. Interaction of MK with other molecules belonging to the renin-angiotensin system, such as AT 2 or mas receptors, remains undefined but unlikely considering that MK is a BK homologue.…”

Section: Discussionmentioning

confidence: 99%

Species-specific pharmacology of maximakinin, an amphibian homologue of bradykinin: putative prodrug activity at the human B₂receptor and peptidase resistance in rats

Charest‐Morin

Bachelard

Jean

et al. 2017

PeerJ

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Maximakinin (MK), an amphibian peptide possessing the C-terminal sequence of bradykinin (BK), is a BK B2 receptor (B2R) agonist eliciting prolonged signaling. We reinvestigated this 19-mer for species-specific pharmacologic profile, in vivo confirmation of resistance to inactivation by angiotensin converting enzyme (ACE), value as a module for the design of fusion proteins that bind to the B2R in mammalian species and potential activity as a histamine releaser. Competition of the binding of [3H]BK to recombinant human myc-B2Rs in cells that express these receptors revealed that MK possessed a tenuous fraction (<0.1%) of the affinity of BK, despite being only ∼20-fold less potent than BK in a contractility assay based on the human isolated umbilical vein. These findings are reconciled by the generation of C-terminal fragments, like Lys-Gly-Pro-BK and Gly-Pro-BK, when the latent MK is incubated with human venous tissue (LC-MS), supporting activation via hydrolysis upstream of the BK sequence. At the rat recombinant myc-B2R, MK had a lesser affinity than that of BK, but with a narrower margin (6.2-fold, radioligand binding competition). Accordingly, MK (10 nM) stimulated calcium transients in cells that expressed the rat receptors, but not the human B2R. Recombinant MRGPRX2, a receptor that mediates cationic peptide-induced mast cell secretion, minimally responded by increased [Ca+2]i to MK at 10 µM. Enhanced green fluorescent protein fused to MK (EGFP-MK) labeled cells that expressed rat, but not human B2Rs. Intravenous MK induced dose-dependent hypotensive, vasodilator and tachycardic responses in anesthetized rats and the effects were antagonized by pretreatment with icatibant but not modified by pyrilamine or enalaprilat. Strong species-specific responses to the toxin-derived peptide MK and its prodrug status in the isolated human vein were evidenced. Accordingly, MK in the EGFP-MK fusion protein is a pharmacophore module that confers affinity for the rat B2R, but not for the human form of the B2R. MK is unlikely to be an efficient mast cell activator, but its resistance to inactivation by ACE was confirmed in vivo.

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Les récepteurs de l'angiotensine II dans le placenta humain sont de type AT₁

Cited by 35 publications

References 17 publications

Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Local Renin-Angiotensin System in the Reproductive System

Species-specific pharmacology of maximakinin, an amphibian homologue of bradykinin: putative prodrug activity at the human B₂receptor and peptidase resistance in rats

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Les récepteurs de l'angiotensine II dans le placenta humain sont de type AT1

Cited by 35 publications

References 17 publications

Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Local Renin-Angiotensin System in the Reproductive System

Species-specific pharmacology of maximakinin, an amphibian homologue of bradykinin: putative prodrug activity at the human B2receptor and peptidase resistance in rats

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Les récepteurs de l'angiotensine II dans le placenta humain sont de type AT₁

Species-specific pharmacology of maximakinin, an amphibian homologue of bradykinin: putative prodrug activity at the human B₂receptor and peptidase resistance in rats