4-chloro-orto-cresol activates ryanodine receptor more selectively and potently than 4-chloro-meta-cresol.

In this study we performed the comprehensive pharmacological analysis of two stereoisomers of 4-chloro-meta-cresol (4CMC), a popular ryanodine receptor (RyR) agonist used in muscle research. Experiments investigating the Ca-releasing action of the isomers demonstrated that the most potent isomer was 4-chloro-orto-cresol (4COC) (EC = 55 ± 14 μM), although 3-chloro-para-cresol (3CPC) was more effective, as it was able to induce higher magnitude of Ca flux from isolated terminal cisterna vesicles. Nevertheless, 3CPC stimulated the hydrolytic activity of the sarcoplasmic reticulum ATP-ase (SERCA) with an EC of 91 ± 17 μM, while 4COC affected SERCA only in the millimolar range (IC = 1370 ± 88 μM).

The diamide insecticide chlorantraniliprole increases the single-channel current activity of the mammalian skeletal muscle ryanodine receptor.

Very recently, the diamide insecticide chlorantraniliprole was shown to induce Ca2+-release from sarcoplasmic reticulum (SR) vesicles isolated from mammalian skeletal muscle through the activation of the SR Ca2+ channel ryanodine receptor. As this result raises severe concerns about the safety of this chemical, we aimed to learn more about its action. To this end, single-channel analysis was performed, which showed that chlorantraniliprole induced high-activity bursts of channel opening that accounts for the Ca2+-releasing action described before.

Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different ways in P-glycoprotein-positive and negative cancer cells.

Aim: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells.

Methods: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) were measured in the same cell lines.