scholarly journals Angiotensin-converting enzyme governs endogenous opioid signaling and synaptic plasticity in nucleus accumbens

2021 ◽  
Author(s):  
Brian H. Trieu ◽  
Bailey C. Remmers ◽  
Carlee Toddes ◽  
Dieter D. Brandner ◽  
Wei Xie ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Angiotensin Converting Enzyme ◽  
Glutamate Release ◽  
Ace Inhibition ◽  
Receptor Activation ◽  
Projection Neurons ◽  
Converting Enzyme ◽  
Endogenous Opioid ◽  
Central Function ◽  
Opioid Signaling

AbstractAngiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is expressed at uniquely high levels in the striatonigral pathway, but its central function remains poorly understood. We find that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced mu opioid receptor activation by Met-enkephalin-Arg-Phe, causing a cell type-specific long-term depression of glutamate release onto medium spiny projection neurons expressing the Drd1 dopamine receptor. Systemic ACE inhibition was not intrinsically rewarding, but decreased the conditioned place preference caused by fentanyl administration, and enhanced reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit, while mitigating risk of addiction.

The protective effect of angiotensin converting enzyme inhibition in experimental renal fibrosis in mice is not mediated by bradykinin B2 receptor activation

2003 ◽  
Vol 89 (04) ◽  
pp. 735-740 ◽  
Author(s):  
Joost Schanstra ◽  
Johan Duchene ◽  
Laurence Desmond ◽  
Eric Neau ◽  
Denis Calise ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renal Fibrosis ◽  
Ace Inhibition ◽  
Receptor Activation ◽  
Tubulointerstitial Fibrosis ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Bradykinin B2 Receptor ◽  
Renal Tubulointerstitial Fibrosis ◽  
At1 Receptor Antagonists

SummaryUnilateral ureteral obstruction (UUO) is an animal model of accelerated renal tubulointerstitial fibrosis. We have recently shown, using this model, that mice lacking the bradykinin B2-receptor (B2-/- ) were more susceptible than control animals to the development of tubulointerstitial fibrosis. Angiotensin converting enzyme (ACE) inhibition slows down UUO-induced renal fibrosis. Since ACE-inhibition increases bradykinin and decreases angiotensin II concentrations we have verified if bradykinin is involved in the antifibrotic effects of ACE-inhibition using the UUO-model and B2-/- mice. Surprisingly, although ACE-inhibition significantly reduced renal fibrosis, no difference was observed between the degree of tubulointerstitial fibrosis, macrophage infiltration and cell proliferation between ACE-inhibitor treated B2+/+ and B2-/- mice suggesting the absence of a role of the B2-receptor in the antifibrotic effects of ACE-inhibition. This was confirmed at the level of bradykinin-induced activity of enzymes involved in the degradation of the extracellular matrix. However in both mouse strains, ACE-inhibitors were more efficient than AT1 receptor antagonists.Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Angiotensin-converting enzyme (ACE)-inhibition in cirrhosis

1993 ◽  
Vol 17 (1) ◽  
pp. 40-47 ◽  
Author(s):  
V. Gross ◽  
E. Treher ◽  
K. Haag ◽  
W. Neis ◽  
U. Wiegand ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibition ◽  
Converting Enzyme

Effect of angiotensin-converting-enzyme inhibition on bradykinin metabolism by vascular endothelial cells

1993 ◽  
Vol 264 (5) ◽  
pp. H1493-H1497 ◽  
Author(s):  
M. Grafe ◽  
C. Bossaller ◽  
K. Graf ◽  
W. Auch-Schwelk ◽  
C. R. Baumgarten ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Vascular Endothelial Cells ◽  
Ace Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Concentration Dependent Manner ◽  
Cell Monolayers ◽  
Converting Enzyme Inhibition

The degradation of bradykinin by angiotensin-converting-enzyme (ACE) activity in cultured human endothelial cells was studied by direct measurement of bradykinin and by its effect on the release of endothelium-derived relaxing factors. The half-life of exogenous bradykinin (10,000 pg/ml) was calculated from the decay of the bradykinin concentration as 46 +/- 2 min in cell monolayers, 133 +/- 15 min in conditioned medium, and 24 +/- 2 min in homogenates. Most of the bradykinin-degrading activity in cell monolayers could be inhibited in a concentration-dependent manner by the ACE inhibitors lisinopril, ramiprilat, and captopril. Bradykinin-degrading activity was released into the culture medium containing one-fourth of the bradykinin-degrading activity found in the presence of cell monolayers. In cell homogenates higher unspecific bradykinin-degrading activities were present. The functional consequence of bradykinin degradation was demonstrated by the potentiating effect of ramiprilat on the generation of endothelium-derived relaxing factors nitric oxide and prostacyclin from endothelial cells. The study supports the concept of increased vasodilatory effects of bradykinin during ACE inhibition.

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