Stereoselective protection of exogenous and endogenous atrial natriuretic factor by enkephalinase inhibitors in mice and humans.

@article{Lecomte1990StereoselectivePO,
  title={Stereoselective protection of exogenous and endogenous atrial natriuretic factor by enkephalinase inhibitors in mice and humans.},
  author={J. Lecomte and P. Baumer and C. Lim and J. Duchier and A. Cournot and J. Dussaule and R. Ardaillou and C. Gros and B. Chaignon and A. Souque},
  journal={European journal of pharmacology},
  year={1990},
  volume={179 1-2},
  pages={
          65-73
        }
}
We compared the relative potencies of sinorphan and retorphan, the S- and R-enantiomers of acetorphan a potent inhibitor of enkephalinase (EC 3.4.34.11), to inhibit membrane metalloendopeptidase in vivo and to protect exogenous and endogenous ANF after oral administration. In mice, sinorphan was 2-3 fold as potent as retorphan in inhibiting the specific in vivo binding of [3H]acetorphan to kidney enkephalinase. The same potency ratio was found for the enhancement of trichloroacetic acid… Expand
Inactivation of atrial natriuretic factor in mice in vivo: crucial role of enkephalinase (EC 3.4.24.11).
TLDR
The crucial role of enkephalinase in ANF inactivation in vivo suggests that inhibitors of this peptidase could be used in a novel therapeutic approach to cardiovascular or renal diseases by protecting endogenous ANF. Expand
Renal and antihypertensive effects of neutral endopeptidase inhibition in transgenic rats with an extra renin gene.
TLDR
Data indicate a beneficial pharmacological profile of neutral endopeptidase inhibition that could prove useful in the treatment of cardiovascular diseases like hypertension. Expand
Enkephalinase (EC 3.4.24.11) inhibitors: protection of endogenous ANF against inactivation and potential therapeutic applications.
Atrial natriuretic factor (ANF) is a cardiac hormone exerting potent cardiovascular and renal effects but its poor intestinal absorption and rapid inactivation have prevented so far its therapeuticExpand
Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites.
TLDR
Enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism, suggesting that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascite. Expand
Degradation of atrial natriuretic factor in mouse blood in vitro and in vivo: Role of enkephalinase (EC 3.4.24.11)
TLDR
Although the peptidase is present in blood plasma and cells, its rate-limiting participation in the clearance of the hormone in vivo does not occur at the blood level, and its half-life is much shorter than that of 125I-ANF. Expand
A Comprehensive Review of the Pharmacodynamics, Pharmacokinetics, and Clinical Effects of the Neutral Endopeptidase Inhibitor Racecadotril
TLDR
Racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. Expand
Prolonged inhibition of neutral endopeptidase 24.11 by sinorphan in stroke-prone spontaneously hypertensive rats.
TLDR
It is demonstrated that long-term NEP inhibition with sinorphan has inhibitory effects on malignant hypertension and associated cardiac hypertrophy in young SHR-SP on a high-sodium diet. Expand
Prolonged neutral endopeptidase inhibition in heart failure.
TLDR
In rats with heart failure, SCH 39370 elevated the high plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) levels 2-fold both initially and at the end of the experiment, which suggests NEP inhibitors may provide a new tool for treating chronic heart failure. Expand
Enhanced natriuretic response to neutral endopeptidase inhibition in patients with moderate chronic renal failure.
TLDR
It is concluded that the marked natriuretic effects of acute NEP inhibition seen in normal subjects are enhanced in the presence of moderate CRF and sustained even in severe renal impairment. Expand
Effects of neutral endopeptidase inhibition and combined angiotensin converting enzyme and neutral endopeptidase inhibition on angiotensin and bradykinin peptides in rats.
TLDR
Data indicate that summation of the effects of separate NEP and ACE inhibition provides the basis for the therapeutic efficacy of their combination, and that increased Ang II levels in plasma and lung may compromise the therapeutic effects of combined NEP/ACE inhibition. Expand
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References

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Protection of atrial natriuretic factor against degradation: diuretic and natriuretic responses after in vivo inhibition of enkephalinase (EC 3.4.24.11) by acetorphan.
  • C. Gros, A. Souque, +4 authors J. Lecomte
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1989
TLDR
Results indicate that enkephalinase plays a critical role in ANF degradation in vivo and that its inhibition enhances the levels of circulating endogenous ANF, which, in turn, results in diuresis and natriuresis. Expand
Diuretic and natriuretic responses in rats treated with enkephalinase inhibitors.
TLDR
Rat atrial natriuretic factor is hydrolysed by pure enkephalinase in vitro at a rate similar to that of 125I-hANF, indicating that the exogenous hormone was protected against degradation and thereby enhance the typical renal effects of the hormone. Expand
Inactivation of atrial natriuretic factor in mice in vivo: crucial role of enkephalinase (EC 3.4.24.11).
TLDR
The crucial role of enkephalinase in ANF inactivation in vivo suggests that inhibitors of this peptidase could be used in a novel therapeutic approach to cardiovascular or renal diseases by protecting endogenous ANF. Expand
Enantiomers of thiorphan and acetorphan: correlation between enkephalinase inhibition, protection of endogenous enkephalins and behavioral effects.
TLDR
Both Thiorphan enantiomers ensured a complete protection of endogenous (Met5)enkephalin released by depolarization and a suppression of the increase in the extracellular levels of Tyr-gly-Gly, a characteristic enkephaline metabolite. Expand
Pharmacological properties of acetorphan, a parenterally active "enkephalinase" inhibitor.
TLDR
Parenteral acetorphan elicited a series of naloxone-reversible, opioid-like effects, most of which were described previously with intracerebral Thiorphan or other enkephalinase inhibitors. Expand
Specific inhibitors of endopeptidase 24.11 inhibit the metabolism of atrial natriuretic peptides in vitro and in vivo
TLDR
Thiorphan afforded almost complete protection against inactivation of ANPs by a renal brush border membrane preparation, and specific inhibitors of endopeptidase 24.11 decrease the degradation of AnPs in vitro, and are effective in reducing the metabolism of ANP-(103-126) in vivo. Expand
Evaluation of enkephalinase inhibition in the living mouse, using [3H]acetorphan as a probe.
TLDR
A novel in vivo binding test was developed in order to evaluate the degree of occupancy of enkephalinase (EC 3.4.24.11), a membrane-bound metallopeptidase, in cerebral and peripheral tissues of mice treated with enkePHalinase inhibitors and indicated a selective labeling of the peptidase. Expand
SCH 39370, a neutral metalloendopeptidase inhibitor, potentiates biological responses to atrial natriuretic factor and lowers blood pressure in desoxycorticosterone acetate-sodium hypertensive rats.
TLDR
The results suggest that NEP can play a role in ANF disposition in vivo and that potentiation of the biological activities of high doses of ANF by SCH 39370 may be consequent to its inhibitory effect on ANF degradation. Expand
Thiorphan and analogs: lack of correlation between potency to inhibit ‘enkephalinase A’ in vitro and analgesic potency in vivo L.G. Mendelsohn, B.G. Johnson, W.L. Scott and R.C.A. Frederickson, J. Pharmacol. exp. Ther., 234 (1985) 386–390
TLDR
Observations suggest that inhibitors of enkephalinase A produce analgesia through a pharmacological mechanism which is not directly related to inhibition of en kephalin degradation. Expand
The Renal Response to Acute Hypervolemia is Caused by Atrial Natriuretic Peptides
Summary: In anesthetized rats, synthetic rat atriopeptin II produced an increase in urinary volume and sodium excretion as well as a decrease in arterial blood pressure. Both the natriuretic andExpand
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