Erklärung für Kontroverse bei Pyrethroid-Studien

[Lucca]

In Vergangenheit gab es Kontroversen bei verschiedenen Pyrethroid-Studien. Eine aktuelle Studie
bringt eine Erklärung dafür und neue wissenschaftliche Erkenntnisse:


Allethrin Differentially Modulates Voltage-Gated Calcium Channel Subtypes in Rat PC12 Cells

Neal AP, Yukun Y, Atchison WD.

Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824-1317.

Toxicol Sci. 2010 May 13.

Abstract

Pyrethroid insecticides are one of the most widely-used classes of insecticides. Previous studies revealed that pyrethroids potently affect the insect voltage-gated sodium channel (VGSC), resulting in prolonged channel open time. However, recent findings have suggested that pyrethroids may affect targets other than the VGSC. In particular, several studies have shown that pyrethroids can modulate the activity of voltage-gated calcium (Ca(2+)) channels (VGCCs). However, these studies often reported conflicting results; some studies observed stimulatory while others inhibitory effects of pyrethroids on VGCCs. The present study investigated whether allethrin (AL), a well-characterized type I pyrethroid, altered VGCC characteristics measured by whole-cell recording in rat pheochromocytoma cells (PC12) differentiated with nerve growth factor (NGF). AL (5 muM) increased peak, end, and tail composite VGCC current independent of its effects on VGSCs. After blocking VGCC subtype-specific current with omega-conotoxin GVIA (GVIA, an N-type VGCC antagonist) or nimodipine (NIM, an L-type VGCC antagonist), our data further suggest that AL differentially affects VGCC subtypes. Thus AL apparently stimulated GVIA-insensitive current while inhibiting NIM-insensitive current. AL also significantly altered the voltage-dependency of activation and inactivation of L-type VGCCs. The differential modulation of VGCC subtypes by AL may explain some of the conflicting observations of other studies.

http://www.ncbi.nlm.nih.gov/pubmed/20466778