Abstract The leptin-melanocortin pathway is playing a pivotal role for central body weight regulation. melanocortin 4 receptor (MC4R) essential to induce satiety after activation by the endogenous ligands α-/β-melanocyte-stimulating hormone. relevance of biased signaling exemplified an MC4R agonist, which has been approved treatment rare forms monogenic obesity. Here discussed as new option dev...

Many drugs that target G-protein-coupled receptors (GPCRs) induce or inhibit their signal transduction with different strengths, which affect their therapeutic properties. However, the mechanism underlying the differences in the signalling levels is still not clear, although several structures of GPCRs complexed with ligands determined by X-ray crystallography are available. Here we utilized NM...

Nebivolol, a third generation β-adrenoceptor (β-AR) antagonist (β-blocker), causes vasodilation by inducing nitric oxide (NO) production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacolog...

Introduction: The ginger rhizome has been widely used in traditional medicine for treatment of gastrointestinal diseases. In the present study the effect of ginger alcoholic extract on mechanical activity of isolated jejunum of male rats and also its interaction with cholinergic, adrenergic and Nitrergic systems were investigated. Methods: Seven adult male Wistar rats were anesthetized by et...

The potential role of adrenergic systems in regulating Na(+) uptake in zebrafish (Danio rerio) larvae was investigated. Treatment with isoproterenol (a generic β-adrenergic receptor agonist) stimulated Na(+) uptake, whereas treatment with phenylephrine (an α(1)-adrenergic receptor agonist) as well as clonidine (an α(2)-adrenergic receptor agonist) significantly reduced Na(+) uptake, suggesting ...

The limiting component within the receptor-G protein-effector complex in airway smooth muscle (ASM) for β(2)-adrenergic receptor (β(2)-AR)-mediated relaxation is unknown. In cardiomyocytes, adenylyl cyclase (AC) is considered the "bottleneck" for β-AR signaling, and gene therapy trials are underway to increase inotropy by increasing cardiac AC expression. We hypothesized that increasing AC in A...

Breast cancer is the most frequent malignancy in women. Several reports demonstrated that adrenergic receptors (ARs) are involved in breast cancer. Here we observed that epinephrine (Epi), an endogenous AR agonist, caused opposite effects in non-tumorigenic (MCF-10A and HBL-100) and tumor cells (MCF-7 and MDA-MB-231). Thus, Epi, in non-tumor breast cells, as well as isoproterenol (β-agonist), i...

Plasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor β (TGF-β)-induced ep...

BACKGROUND Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO(4)) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO(4) has been demonstrated, little is known of the role of inhaled MgSO(4). OBJECTIVES To determine the efficacy of inhaled MgSO(4...

Agonists at the µ-opioid receptor are known to produce potent analgesic responses in the clinical setting, therefore, an increased understanding of the molecular interactions of ligands at this receptor could lead to improved analgesics. As historically morphine has been shown to be a poor recruiter of β-arrestin in recombinant cell systems and this can be overcome by the co-expression of GRK2,...