Aquaporins (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Aquaporins and aquaglyceroporins are membrane channels that allow the permeation of water and certain other small solutes across the cell membrane, or in the case of AQP6, AQP11 and AQP12A, intracellular membranes, such as vesicles and the endoplasmic reticulum membrane [9]. Since the isolation and cloning of the first aquaporin (AQP1) [10], 12 additional mammalian members of the family have been identified, although little is known about the functional properties of one of these (AQP12A; Q8IXF9) and it is thus not tabulated. The other 12 aquaporins can be broadly divided into three families: orthodox aquaporins (AQP0,-1,-2,-4,-5, -6 and -8) permeable mainly to water, but for some additional solutes [2]; aquaglyceroporins (AQP3,-7 -9 and -10), additionally permeable to glycerol and for some isoforms urea [8], and superaquaporins (AQP11 and 12) located within cells [5]. Some aquaporins also conduct ammonia and/or H2O2 giving rise to the terms 'ammoniaporins' ('aquaammoniaporins') and 'peroxiporins', respectively. Aquaporins are impermeable to protons and other inorganic and organic cations, with the possible exception of AQP1 [8]. One or more members of this family of proteins have been found to be expressed in almost all tissues of the body [reviewed in Yang (2017) [13]]. AQPs are involved in numerous processes that include systemic water homeostasis, adipocyte metabolism, brain oedema, cell migration and fluid secretion by epithelia and loss of function mutations of some human AQPs, or their disruption by autoantibodies further underscore their importance [reviewed by Verkman et al. (2014) [12], Kitchen et al. (2105) [8]]. Functional AQPs exist as homotetramers that are the water conducting units wherein individual AQP subunits (each a protomer) have six transmembrane helices and two half helices that constitute a seventh 'pseudotransmembrane domain' that surrounds a narrow water conducting channel [9]. In addition to the four pores contributed by the protomers, an additional hydrophobic pore exists within the center of the complex [9] that may mediate the transport of gases (e.g. O2, CO2, NO) and cations (the central pore is the proposed transport pathway for cations through AQP1) by some AQPs [4, 6]. Although numerous small molecule inhibitors of aquaporins, particularly APQ1, have been reported primarily from Xenopus oocyte swelling assays, the activity of most has subsequently been disputed upon retesting using assays of water transport that are less prone to various artifacts [3] and they are therefore excluded from the tables [see Tradtrantip et al. (2017) [11] for a review]

Promoting Social Justice through Service-Learning in Urban Teacher Education: The Role of Student Voice

Although service-learning is becoming more common in teacher education programs (Anderson & Erickson 2003), few detailed case descriptions show how service-learning can help to promote a social justice orientation for prospective teachers. A comparative descriptive analysis of projects within two teacher preparation programs--one focused on training undergraduates and one focused on training graduate students--illustrates how service-learning, when undergirded by student voice work, prepares prospective educators to teach for social justice in urban classrooms. We identify commonalities in our two approaches to integrating service-learning and student voice into the teacher education curriculum, and we show how our distinctive efforts support prospective teachers in developing the relationships, reflections, and practices they need to become effective educators of urban youth

Search for domain wall dark matter with atomic clocks on board global positioning system satellites

Cosmological observations indicate that 85% of all matter in the Universe is dark matter (DM), yet its microscopic composition remains a mystery. One hypothesis is that DM arises from ultralight quantum fields that form macroscopic objects such as topological defects. Here we use GPS as a ~ 50,000 km aperture DM detector to search for such defects in the form of domain walls. GPS navigation relies on precision timing signals furnished by atomic clocks hosted on board GPS satellites. As the Earth moves through the galactic DM halo, interactions with topological defects could cause atomic clock glitches that propagate through the GPS satellite constellation at galactic velocities ~ 300 km/s. Mining 16 years of archival GPS data, we find no evidence for DM in the form of domain walls at our current sensitivity level. This allows us to improve the limits on certain quadratic scalar couplings of domain wall DM to standard model particles by several orders of magnitude.Comment: 7 pages (main text), and 12 pages for Supplementary Information. v3: Update titl

Inhibitors of Mammalian Aquaporin Water Channels

Aquaporins (AQPs) are water channel proteins that are essential to life, being expressed in all kingdoms. In humans, there are 13 AQPs, at least one of which is found in every organ system. The structural biology of the AQP family is well-established and many functions for AQPs have been reported in health and disease. AQP expression is linked to numerous pathologies including tumor metastasis, fluid dysregulation, and traumatic injury. The targeted modulation of AQPs therefore presents an opportunity to develop novel treatments for diverse conditions. Various techniques such as video microscopy, light scattering and fluorescence quenching have been used to test putative AQP inhibitors in both AQP-expressing mammalian cells and heterologous expression systems. The inherent variability within these methods has caused discrepancy and many molecules that are inhibitory in one experimental system (such as tetraethylammonium, acetazolamide, and anti-epileptic drugs) have no activity in others. Some heavy metal ions (that would not be suitable for therapeutic use) and the compound, TGN-020, have been shown to inhibit some AQPs. Clinical trials for neuromyelitis optica treatments using anti-AQP4 IgG are in progress. However, these antibodies have no effect on water transport. More research to standardize high-throughput assays is required to identify AQP modulators for which there is an urgent and unmet clinical need

Aquaporins in GtoPdb v.2021.3

Aquaporins and aquaglyceroporins are membrane channels that allow the permeation of water and certain other small solutes across the cell membrane, or in the case of AQP6, AQP11 and AQP12A, intracellular membranes, such as vesicles and the endoplasmic reticulum membrane [16]. Since the isolation and cloning of the first aquaporin (AQP1) [20], 12 additional mammalian members of the family have been identified, although little is known about the functional properties of one of these (AQP12A; Q8IXF9) and it is thus not tabulated. The other 12 aquaporins can be broadly divided into three families: orthodox aquaporins (AQP0,-1,-2,-4,-5, -6 and -8) permeable mainly to water, but for some additional solutes [4]; aquaglyceroporins (AQP3,-7 -9 and -10), additionally permeable to glycerol and for some isoforms urea [14], and superaquaporins (AQP11 and 12) located within cells [12]. Some aquaporins also conduct ammonia and/or H2O2 giving rise to the terms 'ammoniaporins' ('aquaammoniaporins') and 'peroxiporins', respectively. Aquaporins are impermeable to protons and other inorganic and organic cations, with the possible exception of AQP1, although this is controversial [14]. One or more members of this family of proteins have been found to be expressed in almost all tissues of the body [reviewed in Yang (2017) [26]]. AQPs are involved in numerous processes that include systemic water homeostasis, adipocyte metabolism, brain oedema, cell migration and fluid secretion by epithelia. Loss of function mutations of some human AQPs, or their disruption by autoantibodies further underscore their importance [reviewed by Verkman et al. (2014) [23], Kitchen et al. (2105) [14]]. Functional AQPs exist as homotetramers that are the water conducting units wherein individual AQP subunits (each a protomer) have six TM helices and two half helices that constitute a seventh 'pseudotransmembrane domain' that surrounds a narrow water conducting channel [16]. In addition to the four pores contributed by the protomers, an additional hydrophobic pore exists within the center of the complex [16] that may mediate the transport through AQP1. Although numerous small molecule inhibitors of aquaporins, particularly APQ1, have been reported primarily from Xenopus oocyte swelling assays, the activity of most has subsequently been disputed upon retesting using assays of water transport that are less prone to various artifacts [5] and they are therefore excluded from the tables [see Tradtrantip et al. (2017) [22] for a review]

Human aquaporins: regulators of transcellular water flow

Background: Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistentwith their expression in most tissues, AQPs are associatedwith diverse physiological and pathophysiological processes. Scope of review: AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell volumeregulation (CVR) is particularly notable. This reviewexamines the regulatory role of AQPs in transcellular water flow, especially in CVR.We focus on key systems of the human body, encompassing processes as diverse as urine concentration in the kidney to clearance of brain oedema. Major conclusions: AQPs are crucial for the regulation of water homeostasis, providing selective pores for the rapidmovement ofwater across diverse cellmembranes and playing regulatory roles in CVR. Gatingmechanisms have been proposed for human AQPs, but have only been reported for plant andmicrobial AQPs. Consequently, it is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane water permeability and a regulator of transcellular water flow. General significance: Elucidating the mechanisms that regulate transcellular water flow will improve our understanding of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins

The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p

Effects of salinity and wet–dry treatments on C and N dynamics in coastal-forested wetland soils: Implications of sea level rise

Forested wetlands dominated by baldcypress (Taxodium distichum) and water tupelo (Nyssa aquatica) are commonly found in coastal regions of the southeastern United States. Global climate change and in particular sea level rise will alter the frequency and magnitude of wet/dry periods and salinity levels in these ecosystems. Soil microcosm experiments were set up to identify the effects of water level variations (0.4–3.0 g-water g-soil−1) and salinity changes (0, 1 and 5 ppt of NaCl) on greenhouse gas emissions (CH4, CO2, and N2O) and dissolved organic carbon (DOC) characteristics from forested wetland soils. Our results indicate that, the effect of water level was much greater than salt intrusion on C and N cycling. Wet–dry treatments significantly decreased DOC production and total CH4-C loss, aromatic and humic-like substance compounds in DOC were increased in both flooding and wet–dry treatments after 60-d incubation. The molecular weight (MW) of DOC, as indicated by E2/E3 ratio and spectral slope, after flooding treatments was higher than that in wet–dry treatments. A first order kinetic model showed there was a positive linear correlation (r2 = 0.73) between CO2 emission rate and DOC concentration which indicated that CO2was mainly generated from DOC. An exponential kinetic model was applied to describe the correlation between CH4 emission rate and DOC concentration (r2 = 0.41). This study demonstrates that an increase in salinity, and in particular variations in wet–dry cycles, will lead to changes in the formation of climate-relevant greenhouse gases, such as CH4, CO2, and N2O