Article abstract
Nature Cell Biology 10, 1421 - 1430 (2008)
Published online: 2 November 2008 | doi:10.1038/ncb1801
Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic 
cells
Thomas F.J. Wagner1,2, Sabine Loch1,2,6, Sachar Lambert1,2,6, Isabelle Straub1,2,4, Stefanie Mannebach2, Ilka Mathar2, Martina Düfer3, Annette Lis2,5, Veit Flockerzi2, Stephan E. Philipp2 & Johannes Oberwinkler1,2
Abstract
Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing 
cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.
- Emmy Noether Research Group Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany.
- Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany.
- Pharmazeutisches Institut, Pharmakologie und Toxikologie Universität Tübingen, 72076 Tübingen, Germany.
- Currrent address: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, Härtelstrasse 16/18, D-04107 Leipzig, Germany.
- Current address: Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii, Honolulu, HI 96813, USA.
- These authors contributed equally to this work.
Correspondence to: Johannes Oberwinkler1,2 e-mail: johannes.oberwinkler@uniklinikum-saarland.de
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