Aquaporin-1 Transports NO Across Cell Membranes

Abstract

Abstract-NO plays a role in the regulation of blood pressure through its effects on renal, cardiovascular, and central nervous system function. It is generally thought to freely diffuse through cell membranes without need for a specific transporter. The water channel aquaporin-1 transports low molecular weight gases in addition to water and is expressed in cells that produce or are the targets of NO. Consequently, we tested the hypothesis that aquaporin-1 transports NO.In cells expressing aquaporin-1, NO permeability correlated with water permeability. NO transport was reduced by 71% by HgCl 2 , an inhibitor of aquaporin-1. Transport of NO by aquaporin-1 saturated at 3 mol/L NO and displayed a K 1/2 (the concentration of NO that produces half of the maximum transport rate) of 0.54 mol/L. Reconstitution of purified aquaporin-1 into lipid vesicles increased NO influx by 316%. In endothelial cells, lowering aquaporin-1 expression with a small interfering RNA (siRNA) blunted aquaporin-1 expression by 54% and NO release by 44%. We conclude that NO transport by aquaporin-1 may allow cells to control intracellular NO levels and effects. NO transport by aquaporin-1 may play a role in central nervous system, vascular and renal function, and consequently blood pressure. Disruption of NO transport by aquaporin-1 offers an alternate cause for diseases currently explained by inadequate NO bioavailability.

Relative CO 2 /NH 3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

“…The less hydrophilic CO 2 , however, could move through the hydrophobic central pores of all 5 channels. NO is also known to move through AQP1 (8), and indirect evidence is consistent with the idea that O 2 moves Indices of channel-dependent NH 3 permeability. We computed (⌬pHS*)NH3 using the same approach as in A.…”

“…Molecular dynamics simulations suggest that CO 2 can pass through the 4 aquapores of an AQP1 tetramer (7) and especially through the central pore between the 4 monomers (7). Additional data indicate that AQP1 is permeable to nitric oxide (8), and that-when expressed in Xenopus oocytes (9,10) or when reconstituted into planar lipid bilayers (11)-AQP1, AQP3, AQP8, AQP9, and the plant aquaporin TIP2;1 are all permeable to NH 3 .…”

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

“…H 2 O 2 , a small and non-charged molecule that is readily produced and removed following these physiological stimuli, exhibits properties that are ideal for signal transduction [2]. Although it was initially believed that H 2 O 2 can freely diffuse across membranes, recent genetic evidence suggests that some membranes are poorly permeable to H 2 O 2, and that its transport may be regulated by aquaporin channel proteins [26,27], which also regulates transport of NO [28]. H 2 O 2 exerts its functions in signaling by causing reversible amino-acid oxidations, as will be discussed below.…”

No facilitator required for membrane transport of hydrogen sulfide

“…Although there is little doubt that they facilitate the membrane transport of NH 3 (18), the contribution of aquaporins to NO, CO 2 , or O 2 transport is under debate (19)(20)(21)(22)(23). At the same time as the permeability of P M,CO 2 ϭ 3.2 cm/s allows CO 2 to pass membranes freely (22), the NH 3 permeability P M,NH 3 ϭ 0.016 cm/s (24) indicates that a cholesterol-containing epithelial membrane acts as a barrier and, consequently, that membrane channels (aquaporin-8) facilitate NH 3 diffusion (18).…”