Stimulation of beta 2-adrenergic receptor increases cystic fibrosis transmembrane conductance regulator expression in human airway epithelial cells through a cAMP/protein kinase A-independent pathway. | LitMetric
PSD-95/Dlg-A/ZO-1 (PDZ) domains play an essential role in determining cell polarity. The Na(+)/H(+) exchanger regulatory factor (NHERF), also known as EBP50, contains two PDZ domains that mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. Moreover, it has been shown that cystic fibrosis transmembrane conductance regulator (CFTR) and beta(2)-adrenergic receptor (beta(2)AR) bind equally well to the PDZ1 domain of EBP50. We hypothesized that beta(2)AR activation may regulate CFTR protein expression. To verify this, we evaluated the effects of a pharmacologically relevant concentration of salmeterol (2.10(-7) m), a long acting beta(2)AR agonist, on CFTR expression in primary human airway epithelial cells (HAEC). beta(2)AR stimulation induced a time-dependent increase in apical CFTR protein expression, with a maximal response reached after treatment for 24 h. This effect was post-transcriptional, dependent upon the beta(2)AR agonist binding to beta(2)AR and independent of the known beta(2)AR agonist-mediated cAMP/PKA pathway. We demonstrated by immunohistochemistry that CFTR, beta(2)AR, and EBP50 localize to the apical membrane of HAEC. Analyses of anti-EBP50 protein immunoprecipitate showed that salmeterol induced an increase in the amount of CFTR that binds to EBP50. These data suggest that beta(2)AR activation regulates the association of CFTR with EBP50 in polarized HAEC.
Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms of PAGly in a rat cerebral ischemia/reperfusion (I/R) injury model.
Background: Recent findings suggest that β3-adrenergic receptors (β3-AR) could play a role in the hemodynamic regulation, but their function in septic shock remains unclear. This study investigates the modulation of β3-AR in an experimental murine model of resuscitated septic shock on in vivo hemodynamic, ex vivo vasoreactivity, inflammation and survival.
Method: Wild-type mice were used, undergoing cecal ligation and puncture (CLP) to induce septic shock, with SHAM as controls.
G-protein-coupled receptors (GPCRs) play a crucial role in modulating physiological responses and serve as the main drug target. Specifically, salmeterol and salbutamol, which are used for the treatment of pulmonary diseases, exert their effects by activating the GPCR β2-adrenergic receptor (β2AR). In our study, we employed coarse-grained molecular dynamics simulations with the Martini 3 force field to investigate the dynamics of drug molecules in membranes in the presence and absence of β2AR.
Chlamydia genital infection caused by Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. A mouse model has been developed in our laboratory to better understand the effect of cold-induced stress on chlamydia genital infection and immune response. However, the stress mechanism affecting the host response to Chlamydia muridarum genital infection remains unclear.
Previous studies have demonstrated that norepinephrine (NE) released during chronic stress promotes breast cancer (BC) metastasis via adrenergic receptors (ARs). However, the effect of NE on tumor-associated macrophage polarization and the underlying mechanisms remain largely unknown. In this study, we aimed to investigate the influence of NE on M2 macrophage polarization, with a particular focus on the crosstalk between macrophages and BC cells.
