Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA2 (cPLA2)and Clara cell secretory protein (CCSP), a modulator of cPLA2 activity, we compared lung injury with and without a PLA2 inhibitor in wild-type mice and CCSP-null mice (CCSP-/-) ventilated with high and low peak inflation pressures (...

Modulation of voltage-gated Ca(2+) channels controls activities of excitable cells. We show that high-voltage activated Ca(2+) channels are regulated by membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) with different sensitivities. Plasma membrane PIP(2) depletion by rapamycin-induced translocation of an inositol lipid 5-phosphatase or by a voltage-sensitive 5-phosphatase (VSP) suppresse...

Carrot (Daucus carota L.) cells plasmolyzed within 30 s after adding sorbitol to increase the osmotic strength of the medium from 0.2 to 0.4 or 0.6 osmolal. However, there was no significant change in the polyphosphorylated inositol phospholipids or inositol phosphates or in inositol phospholipid metabolism within 30 s of imposing the hyperosmotic stress. Maximum changes in phosphatidylinositol...

Phosphatidylinositol4,5-bisphosphate (PIP,) at 0.1 mob% activated the protein kinase C (PKC)-mediated phosphorylation of 87-, 55and 47-kDa brain proteins. Neomycin, an aminoglycoside antibiotic that binds PIP, with a high affinity, inhibited PIP;PKC activity in a concentration-dependent manner. Low concentrations of neomycin (< 2 mM) did not affect DG.PKC activity; however, 4 mM neomycin inhibi...

Inwardly rectifying K(+) (Kir) channels are important regulators of resting membrane potential and cell excitability. The activity of Kir channels is critically dependent on the integrity of channel interactions with phosphatidylinositol 4,5-bisphosphate (PIP(2)). Here we identify and characterize channel-PIP(2) interactions that are conserved among Kir family members. We find basic residues th...

A genetically encoded sensor for parallel measurements of phosphatidylinositol 3-kinase activity and hydrogen peroxide (H(2)O(2)) levels (termed PIP-SHOW) was developed. Upon elevation of local phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) concentration, the sensor translocates from the cytosol to the plasma membrane, while a ratiometric excitation change rapidly and simultaneously reports ...

Division of Translational Toxicology, Department of Epidemiology and Public Health (EFRP, YA, EXA), and Program of Comparative Medicine and Departments of Pathology, Medicine, and Epidemiology and Public Health (LJDT), University of Maryland School of Medicine, Baltimore, MD; Countervail Corporation (EJB, GWB), Charlotte, NC; Biomedical Advanced Research and Development Authority (BARDA) (EJW),...

Gastric vesicles purified from acid-secreting rabbit stomach display K(+) permeability manifested by the valinomycin-independent proton pumping of H(+)-K(+)-ATPase as monitored by acridine orange quenching. This apparent K(+) permeability is attenuated by the treatment of the membrane with 5 mM Mg(2+), and this phenomenon has been attributed to membrane-bound phosphoprotein phosphatase. However...

It has long been believed that the cortical actin cytoskeleton plays an important role in regulating the secretion of hormones and neurotransmitters. In this study, we investigated the control of actin dynamics in primary neuroendocrine cells and determined the relationship of actin dynamics to various components of the secretory response. The amount of cortical f-actin in chromaffin cells was ...

BACKGROUND Health care policy-makers look for prescribing indicators at the population level to evaluate the performance of prescribers, improve quality and control drug costs. The aim of this research was to; (i) estimate the level of variation in potentially inappropriate prescribing (PIP) across prescribers in the national Irish older population using the STOPP criteria; (ii) estimate how re...