Menthol reduces phototoxicity pain in a mouse model of photodynamic therapy.

Phototoxicity-induced pain is a major clinical problem triggered by light acting on photosensitising drugs or endogenous porphyrins, notably protoporphyrin IX (PpIX), an intermediary in heme biosynthesis. Protoporphyrin IX accumulates in individuals with erythropoietic protoporphyria and is elevated during photodynamic therapy subsequent to application of 5-aminolevulinic acid (ALA). Pain occurs during irradiation of PpIX and responds poorly to conventional analgesics.

Influences on blockade by t-butylbicyclo-phosphoro-thionate of GABA(A) receptor spontaneous gating, agonist activation and desensitization.

Picrotoxin and t-butylbicyclophosphorothionate (TBPS) are GABA(A) receptor (GABA(A)R) open channel blockers. However, picrotoxin displaceable [(35)S]TBPS binding to α1β2γ2 GABA(A)Rs occurs in the absence of GABA, suggesting that access to the binding site is independent of activation. Alternatively, spontaneous gating may provide access to the channel.

The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells.

Analysis of membrane currents recorded from hormone-deprived H441 cells showed that the membrane potential (V(m)) in single cells (approximately -80 mV) was unaffected by lowering [Na+]o or [Cl(-)]o, indicating that cellular Na+ and Cl(-) conductances (GNa and GCl, respectively) are negligible. Although insulin (20 nM, approximately 24 h) and dexamethasone (0.2 microM, approximately 24 h) both depolarized Vm by approximately 20 mV, the response to insulin reflected a rise in GCl mediated via phosphatidylinositol 3-kinase (PI3K) whereas dexamethasone acted by inducing a serum- and glucocorticoid-regulated kinase 1 (SGK1)-dependent rise in GNa.