Modulation by alkyl p-hydroxybenzoates of voltage- and ligand-gated channels in peripheral neuronal cells.
Effects of alkyl p-hydroxybenzoates (APHBs), which are used as preservatives, on ion channels were investigated in rat pheochromocytoma PC12 cells. Methyl p-hydroxybenzoate (MPHB; 300 microM) and butyl p-hydroxybenzoate (BPHB; 300 microM) inhibited Ba2+ current passing through Ca2+ channels, and facilitated the inactivation of the Ba2+ current. K+ current obtained with a depolarizing voltage-step was also suppressed by 300 microM MPHB or 300 microM BPHB. The extent of the suppression of the K+ current was not affected by extracellular Cd2+, suggesting that the suppression of the K+ current is not a secondary effect arising from the Ca2+ channel inhibition. An inward current activated by acetylcholine (ACh; 100 microM) was abolished by 300 microM BPHB, and it was partially blocked by 300 microM MPHB. In contrast to the ACh-activated current, an inward current activated by ATP (30 microM) was markedly potentiated by 300 microM BPHB. The results suggest that APHBs exert significant effects on the voltage- and ligand-gated channels. The significance of these channel modifications were discussed in relation to reported effects of APHBs, including induction of minor irritation.
Inoue
K
K
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Nakazawa
K
K
Inoue
K
K
Fujimori
K
K
Takanaka
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D008024:Ligands; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D016716:PC12 Cells; D010226:Parabens / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism
D007473:Ion Channels; D008024:Ligands; D010226:Parabens; D015221:Potassium Channels; D011978:Receptors, Nicotinic; D001464:Barium; C038091:butylparaben; D000255:Adenosine Triphosphate; C015358:methylparaben; D000109:Acetylcholine