Rhône-Poulenc

About: Rhône-Poulenc is a based out in . It is known for research contribution in the topics: Alkyl & Catalysis. The organization has 8909 authors who have published 8934 publications receiving 182241 citations. The organization is also known as: Rhone-Poulenc.

Regulation of tight junction permeability by calcium mediators and cell cytoskeleton in rabbit tracheal epithelium.

Abstract: The present study investigates the mechanisms controlling tight junction permeability of the tracheal epithelium, with an emphasis on the regulatory role of intra- and extracellular calcium as well as the cell cytoskeleton. The tracheas were isolated from rabbits and their junctional permeability barrier was investigated in vitro by means of transepithelial electrical resistance measurements and flux measurements of the radiolabeled paracellular tracer, 14C-mannitol. The effects of intra- and extracellular calcium were studied using the calcium ionophore A 23187 and EGTA, and that of the cytoskeleton was investigated using cytochalasin B. Intracellular calcium of the tracheal epithelium was monitored microfluorometrically using the specific calcium indicator, Fura-2 AM (acetoxymethyl ester). The results indicate that the tight junction permeability of the trachea was significantly increased upon treatment with all three of the test compounds, as evidenced by a substantial decrease in transepithelial electrical resistance and an increase in transepithelial flux of 14C-mannitol. The effects of EGTA and cytochalasin B on the tight junction permeability are fully reversible upon removal of the compounds from the bathing media. On the other hand, tissues treated with the calcium ionophore demonstrate a partial or no recovery in membrane permeability, depending on the intracellular calcium levels. Moderate and transient increases in intracellular calcium caused a partial reversibility of the membrane resistance, while high and sustained intracellular calcium levels induce a complete irreversibility of the membrane resistance. These results suggest that high extracellular calcium levels and low intracellular calcium levels are required for the normal maintenance of the junctional permeability in the tracheal epithelium. Studies using cytochalasin B indicate that there is also a close relationship between the tight junctions and the organization of actin microfilaments. Alterations of these structures as well as cellular calcium levels can result in a substantial change in transepithelial permeability. Therefore compounds that affect tight junction permeability may exert their action through the calcium and cytoskeleton mechanisms.

Isoindolone derivatives, their preparation and pharmaceutical compositions containing them

Abstract: This invention relates to isoindolone derivatives of general formula (I) in which the radicals R are hydrogen atoms or together form a bond, the symbols R' are phenyl radicals which can be substituted by a halogen atom or a methyl radical in position 2 or 3, X is an oxygen or sulphur atom or a radical N--R3, R3 being H, optionally substituted alkyl or dialkylamino, R1 is optionally substituted phenyl or cyclohexadienyl, naphthyl or a heterocycle and R2 is H, halogen, OH, alkyl, amionoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxy, alkylthio, acyloxy, carboxyl, optionally substituted alkoxycarbonyl, benzyloxycarbonyl, amino or acylamino, in their (3aR,7aR) forms or in the (3aRS,7aRS) form or their mixtures, and if appropriate their salts where such exist, and their preparation. The new derivatives according to the invention are particularly valuable as antagonists of substance P. ##STR1##