4-amylcinnamoylanthranilic-acid and 2-aminoethoxydiphenyl-borate

Excessive Ca

Topics: Adenosine Diphosphate Ribose; Animals; Apoptosis; Boron Compounds; Calcium Signaling; Caspases; Cinnamates; Cytokines; Enzyme Activation; Glutathione; Hyperalgesia; Lipid Peroxidation; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Mice, Knockout; Migraine Disorders; Neuroinflammatory Diseases; Neurons; Nitroglycerin; ortho-Aminobenzoates; Oxidative Stress; Phenanthrenes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Trigeminal Ganglion; TRPM Cation Channels

We sought to determine the contribution of oxidative stress-dependent activation of TRPM2 and L-type voltage-gated Ca(2+) channels (VGCC) in dorsal root ganglion (DRG) neurons of rats after spinal cord injury (SCI).. The rats were divided into 4 groups: control; sham control; SCI; and SCI+nimodipine groups. The neurons of the SCI groups were also incubated with non-specific TRPM2 channel blockers, 2-aminoethoxydiphenylborate (2-APB) and N-(p-amylcinnamoyl)anthranilic acid (ACA), before H2 O2 stimulation.. The [Ca(2+) ]i concentrations were higher in the SCI group than in the control groups, although their concentrations were decreased by nimodipine and 2-APB. The H2 O2 -induced TRPM2 current densities in patch-clamp experiments were decreased by ACA and 2-APB incubation. In the nimodipine group, the TRPM2 channels of neurons were not activated by H2 O2 or cumene hydroperoxide.. Increased Ca(2+) influx and currents in DRG neurons after spinal injury indicated TRPM2 and voltage-gated Ca(2+) channel activation.

Topics: Action Potentials; Animals; Boron Compounds; Calcium; Calcium Channels, L-Type; Cinnamates; Disease Models, Animal; Ganglia, Spinal; Hydrogen Peroxide; Male; Neurons; ortho-Aminobenzoates; Oxidants; Patch-Clamp Techniques; Rats; Rats, Wistar; Spinal Cord Injuries; Statistics, Nonparametric; TRPM Cation Channels

Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca(2+)-permeable cation channel and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. TRPM2 current responses are reported to be drastically potentiated by the combination of each of these ligands with heat. Furthermore, the combination of cyclic ADP-ribose with heat also activates TRPM2. Although flufenamic acid, antifungal agents (miconazole and clotrimazole), and a phospholipase A(2) inhibitor (N-(p-amylcinnamoyl)anthranilic acid) inhibit TRPM2, their inhibition was either gradual or irreversible.. To facilitate future research on TRPM2, we screened several compounds to investigate their potential to activate or inhibit the TRPM2 channels using the patch-clamp technique in HEK293 cells, transfected with human TRPM2.. 2-aminoethoxydiphenyl borate (2-APB) exhibited a rapid and reversible inhibition of TRPM2 channels that had been activated by its ADP-ribose or cADP-ribose and heat in a dose-dependent manner (IC(50) about 1 microM). 2-APB also inhibited heat-evoked insulin release from pancreatic islets, isolated from rats.. 2-APB proved to be a powerful and effective tool for studying the function of TRPM2.

Topics: Adenosine Diphosphate Ribose; Animals; Antifungal Agents; Boron Compounds; Cell Line; Cinnamates; Cyclic ADP-Ribose; Dose-Response Relationship, Drug; Flufenamic Acid; Hot Temperature; Humans; In Vitro Techniques; Inhibitory Concentration 50; Insulin; Insulin Secretion; Islets of Langerhans; Male; ortho-Aminobenzoates; Patch-Clamp Techniques; Rats; Rats, Wistar; Transfection; TRPM Cation Channels