New benzodiazepine-based gamma-turn mimetics with one or two amino acid side chains were synthesized. The gamma-turn mimetics were incorporated into angiotensin II (Ang II) replacing the Val(3)-Tyr(4)-Ile(5) or Tyr(4)-Ile(5) peptide segments. All of the resulting pseudopeptides displayed high AT(2)/AT(1) receptor selectivity and exhibited AT(2) receptor affinity in the low nanomolar range. Molecular modeling was used to investigate whether the compounds binding to the AT(2) receptor could position important structural elements in common areas. A previously described benzodiazepine-based gamma-turn mimetic with high affinity for the AT(2) receptor was also included in the modeling. It was found that the molecules, although being structurally quite different, could adopt the same binding mode/interaction pattern in agreement with the model hypothesis. The pseudopeptides selected for agonist studies were shown to act as AT(2) receptor agonists being able to induce outgrowth of neurite cells, stimulate p42/p44(mapk), and suppress proliferation of PC12 cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm0491492 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages.
Cell Rep
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China. Electronic address:
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14 (Fn14), the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is highly induced in myofibroblasts in the lungs of IPF patients and the bleomycin-induced lung fibrosis model.
View Article and Find Full Text PDFHypertension: A Continuing Public Healthcare Issue.
Int J Mol Sci
December 2024
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Hypertension is a cardiovascular disease defined by an elevated systemic blood pressure. This devastating disease afflicts 30-40% of the adult population worldwide. The disease burden for hypertension is great, and it greatly increases the risk of cardiovascular morbidity and mortality.
View Article and Find Full Text PDFPGE and HCN2 ion channels are critical mediators of pain initiated by angiotensin II.
Brain Behav Immun
December 2024
Wolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. Electronic address:
Angiotensin II is well known to have an important influence on blood pressure, mediated via the angiotensin II type 1 receptor (AT1R), but more recent studies have shown that angiotensin II may play an important additional role in eliciting pain via a distinct action at the angiotensin II type 2 receptor (AT2R). Signalling pathways that link activation of AT2R to a sensation of pain are, however, incompletely understood. Here we use rodent inflammatory pain models to confirm that selective activation of AT2R triggers aversive responses, and that these are abolished by either antagonism or genetic deletion of AT2R.
View Article and Find Full Text PDFMelatonin attenuates responses to angiotensin II in isolated aortic rings of STZ-induced type 1-like DM rats.
Endocr Res
December 2024
Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.
Background: In patients with diabetes mellitus (DM), vascular endothelial dysfunction (VED) is the main reason for impaired life expectancy. Melatonin (MEL) demonstrates wide-ranging effects across various organs and exhibits pleiotropic characteristics. The current study aims to investigate the modulatory roles of MEL vascular response to angiotensin II (Ang II) and its receptors including angiotensin type 1 receptor (AT-1 R) and angiotensin type 2 receptor (AT-2 R) in isolated thoracic aorta of non-diabetes (non-DM) and diabetes (DM) rats.
View Article and Find Full Text PDFFasting recovers age-related hypertension in the rats: reset of renal renin-angiotensin system components and klotho.
BMC Nephrol
December 2024
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Article Synopsis
- The study examined how intermittent fasting impacts age-related high blood pressure and the renal renin-angiotensin system in rats.
- Older rats showed higher blood pressure and hormone levels associated with hypertension compared to younger rats, as well as lower levels of α-klotho and kidney receptor proteins.
- Intermittent fasting, especially every other day fasting, effectively lowered blood pressure and improved certain RAS components in older rats, indicating its potential benefits for managing age-related hypertension.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!