Propranolol, a phosphatidate phosphohydrolase inhibitor, also inhibits protein kinase C.

Sozzani, Silvano; Agwu, David E.; McCall, Charles E.; O’Flaherty, Joseph T.; Schmitt, Jens; Kent, Jonathan; McPhail, Linda C.

doi:10.1016/s0021-9258(19)88727-6

Cited by 100 publications

(19 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When β-adrenergic receptor (β 2 -AR) and protein kinase A were blocked by propranolol and KT5720, the bronchodilation effect induced by YG-1 was specifically inhibited. When β 2 -ARand protein kinase A were blocked by propranolol and KT5720 [24], YG-1 induced bronchodilatation was inhibited.…”

Section: Discussionmentioning

confidence: 98%

“…Respiratory disorders, such as asthma and sore throat, induce contraction of airway smooth muscle cells and airway hyperresponsiveness [25]. To alleviate these acute and chronic airway constrictions, β-adrenergic agonists that relax airway smooth muscle cells are usually administered [24]. The mechanism of action of cAMP is to induce airway smooth muscle cell expansion through stimulation of protein kinase A (PKA) [26,27].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

YG-1 Extract Improves Acute Pulmonary Inflammation by Inducing Bronchodilation and Inhibiting Inflammatory Cytokines

et al. 2021

View full text Add to dashboard Cite

YG-1 extract used in this study is a mixture of Lonicera japonica, Arctic Fructus, and Scutellariae Radix. The present study was designed to investigate the effect of YG-1 extract on bronchodilatation (ex vivo) and acute bronchial and pulmonary inflammation relief (in vivo). Ex vivo: The bronchodilation reaction was confirmed by treatment with YG-1 concentration-accumulation (0.01, 0.03, 0.1, 0.3, and 1 mg/mL) in the bronchial tissue ring pre-contracted by acetylcholine (10 μM). As a result, YG-1 extract is considered to affect bronchodilation by increased cyclic adenosine monophosphate, cAMP) levels through the β2-adrenergic receptor. In vivo: experiments were performed in C57BL/6 mice were divided into the following groups: control group; PM2.5 (fine particulate matter)-exposed group (PM2.5, 200 μg/kg/mL saline); and PM2.5-exposed + YG-1 extract (200 mg/kg/day) group. The PM2.5 (200 μg/kg/mL saline) was exposed for 1 h for 5 days using an ultrasonic nebulizer aerosol chamber to instill fine dust in the bronchi and lungs, thereby inducing acute lung and bronchial inflammation. From two days before PM2.5 exposure, YG-1 extract (200 mg/kg/day) was administered orally for 7 days. The PM2.5 exposure was involved in airway remodeling and inflammation, suggesting that YG-1 treatment improves acute bronchial and pulmonary inflammation by inhibiting the inflammatory cytokines (NLRP3/caspase-1 pathway). The application of YG-1 extract with broncho-dilating effect to acute bronchial and pulmonary inflammation animal models has great significance in developing therapeutic agents for respiratory diseases. Therefore, these results can provide essential data for the development of novel respiratory symptom relievers. Our study provides strong evidence that YG-1 extracts reduce the prevalence of respiratory symptoms and the incidence of non-specific lung diseases and improve bronchial and lung function.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

YG-1 Extract Improves Acute Pulmonary Inflammation by Inducing Bronchodilation and Inhibiting Inflammatory Cytokines

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Effect of PA Phosphohydrolase (PAP) and Protein Phosphatase Inhibitots. Human monocytes, U937 cells, and PMN were either not treated or treated with propranolol (200/~M) (39) or calyculin A (100 riM) (40,41), and stimulated with either medium or medium containing IL-4 (10 ng/ml) or FMLP (5 gM). The generation of DAG at 10 min of stimulation was measured and expressed as a percentage of control (medium).…”

Section: Methodsmentioning

confidence: 99%

Interleukin 4 receptor signaling in human monocytes and U937 cells involves the activation of a phosphatidylcholine-specific phospholipase C: a comparison with chemotactic peptide, FMLP, phospholipase D, and sphingomyelinase.

Zhu

et al. 1994

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Interleukin 4 (IL-4) diminishes cytokine activation of human macrophage. IL-4 binding to monocyte IL-4R is associated with protein kinase C (PKC) translocation to a nuclear fraction. The cleavage of diacyglycerol (DAG), an activator of PKC, from membrane phospholipids was investigated to define the proximal events of IL-4R signaling. IL-4 induced a statistically significant time-and dose-dependent generation of DAG. The IL-4-triggered production of DAG was not derived from phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis, since neither cytosolic calcium flux nor liberation of inositol phosphates was detected in response to IL-4. Experiments were performed using [14C- methyl]choline-labeled U937 cells and monocytes to determine whether IL- 4R activated phospholipase C (PLC), PLD, or PLA2 to use membrane phosphatidylcholine (PC) to form DAG. IL-4 induced a time- and dose- dependent increase of phosphocholine (pchol) with concomitant degradation of membrane PC (p < 0.05 compared with control). The finding that the peak reduction of PC was equivalent to peak production of pchol suggested that IL-4R signaling involved the activation of a PC- specific PLC. Changes in choline (chol) or lyso-PC and glycerolphosphocholine, the respective products of PC cleavage by PLD or PLA2, were not detected in IL-4-treated cells. In contrast, exogenous PLD induced an increase in chol and concomitant loss of membrane PC. Additional investigation suggested that IL-4R signaling does not involve PLD. In cells labeled with L-lyso-3-PC 1-[1- 14C]palmitoyl, PLD but not IL-4, increased the production of phosphatidic acid (PA) and phosphatidyl-ethanol when pretreated with ethanol. Propranolol, an inhibitor of phosphatidate phosphohydrolase, and calyculin A, a phosphatase 1 and 2A inhibitor, blocked DAG production in response to FMLP but not to IL-4. In propranolol pretreated cells, PMA but not IL-4 triggered the production of PA and lowered the amount of DAG. Evidence that PLA2 is not coupled to IL-4R is the detection of arachidonate production in response to FMLP but not to IL-4. Furthermore, IL-4R is not coupled to sphingomyelinase (SMase) since IL-4, unlike exogenous SMase, did not generate ceramide but induced the hydrolysis of PC to pchol that was comparable to exogenous PLC. In summary, IL-4R signaling in monocytes and U937 cells involves PLC and not PLD, PLA2, or SMase, and it uses PC and not PIP2 to form DAG.

show abstract

“…It was reported that, in fact, at high doses, PROP can inhibit either phospholipase D or protein kinase C, due to its interactive membrane properties. PROP can act as an amphipathic cationic drug, penetrating the membrane, binding to specific phospholipids and redirecting neutral phospholipid biosynthesis to acidic phospholipids [41,42]. This inhibition was observed at concentrations 100 times higher than that necessary to antagonize the receptor, suggesting that the effect of PROP at high doses is not mediated by β-AR but by its membrane stabilizer properties [42].…”

Section: Discussionmentioning

confidence: 99%

“…PROP can act as an amphipathic cationic drug, penetrating the membrane, binding to specific phospholipids and redirecting neutral phospholipid biosynthesis to acidic phospholipids [41,42]. This inhibition was observed at concentrations 100 times higher than that necessary to antagonize the receptor, suggesting that the effect of PROP at high doses is not mediated by β-AR but by its membrane stabilizer properties [42]. These PROP effects, independent of β-AR, increase the level of complexity for the use of PROP in signal transduction studies.…”

Section: Discussionmentioning

confidence: 99%

Agonist Effects of Propranolol on Non-Tumor Human Breast Cells

Gargiulo

Rivero

Siervi

et al. 2020

Cells

View full text Add to dashboard Cite

The β-blocker propranolol (PROP) has been proposed as a repurposed treatment for breast cancer. The similarity of action between β-agonists and antagonists found on breast cells encouraged us to compare PROP and isoproterenol (ISO, agonist) signaling pathways on a human breast cell line. Cell proliferation was measured by cell counting and DNA-synthesis. Cell adhesion was measured counting the cells that remained adhered to the plastic after different treatments. Changes in actin cytoskeleton were observed by fluorescence staining and Western Blot. ISO and PROP caused a diminution of cell proliferation and an increase of cell adhesion, reverted by the pure β-antagonist ICI-118551. ISO and PROP induced a reorganization of actin cytoskeleton increasing F-actin, p-COFILIN and p-LIMK. While ISO elicited a marked enhancement of cAMP concentrations and an increase of vasodilator-stimulated phosphoprotein (VASP) and cAMP response element-binding protein (CREB) phosphorylation, PROP did not. Clathrin-mediated endocytosis inhibition or β-arrestin1 dominant-negative mutant abrogated PROP-induced cell adhesion and COFILIN phosphorylation. The fact that PROP has been proposed as an adjuvant drug for breast cancer makes it necessary to determine the specific action of PROP in breast models. These results provide an explanation for the discrepancies observed between experimental results and clinical evidence.

show abstract

Propranolol, a phosphatidate phosphohydrolase inhibitor, also inhibits protein kinase C.

Cited by 100 publications

References 70 publications

YG-1 Extract Improves Acute Pulmonary Inflammation by Inducing Bronchodilation and Inhibiting Inflammatory Cytokines

YG-1 Extract Improves Acute Pulmonary Inflammation by Inducing Bronchodilation and Inhibiting Inflammatory Cytokines

Interleukin 4 receptor signaling in human monocytes and U937 cells involves the activation of a phosphatidylcholine-specific phospholipase C: a comparison with chemotactic peptide, FMLP, phospholipase D, and sphingomyelinase.

Agonist Effects of Propranolol on Non-Tumor Human Breast Cells

Contact Info

Product

Resources

About