David S. Miller: Scientist, Mentor, Friend-a tribute and thank you.

David S. Miller was Acting Scientific Director of the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, and Head of the Intracellular Regulation Group in the Laboratory of Toxicology and Pharmacology before he retired in 2016. David received his Ph.

The xenobiotic transporter, MRP2, in epithelia from insects, sharks, and the human breast: implications for health and disease.

A large number of mechanisms, including special excretory transporters, have evolved to help organisms excrete deleterious xenobiotics and endogenous molecules. We have examined the xenobiotic transport function of a putative multidrug resistance associated protein, MRP2, in three different epithelia: the insect renal (Malpighian) tubules, the secretory tubule of the shark rectal gland, and in ductules of the human breast. In the case of the insect and shark, transporter activity occurs in epithelia capable of great fluid transport.

Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress.

The oxidative-stress-induced alteration in paracellular junctional complexes was analysed in Caco-2 cell monolayer. Oxidative stress induced a rapid increase in tyrosine phosphorylation of occludin, zonula occludens (ZO)-1, E-cadherin and beta-catenin. An oxidative-stress-induced decrease in transepithelial electrical resistance was associated with a redistribution of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the intercellular junctions.

Regulation of MRP2-mediated transport in shark rectal salt gland tubules.

We examined endothelin-1 (ET-1) regulation of the xenobiotic efflux pump, multidrug resistance-associated protein isoform 2 (MRP2), in intact dogfish shark rectal salt gland tubules using a fluorescent substrate sulforhodamine 101 and confocal microscopy. Subnanomolar to nanomolar concentrations of ET-1 rapidly reduced the cell-to-lumen transport of sulforhodamine 101. These effects were prevented by an ET(B) receptor antagonist but not by an ET(A) receptor antagonist.