Changes in fluid secretion rate alter net transepithelial transport of MRP2 and P‐glycoprotein substrates in Malpighian tubules of <i>Drosophila melanogaster</i>

O’Donnell, Michael J.; Leader, John P.

doi:10.1002/arch.20148

Cited by 17 publications

(11 citation statements)

References 23 publications

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“…Similarly, TxRd showed increased intracellular concentrations with increasing concentrations the MRP inhibitor MK571 (Luna-Tortos et al, 2010; Zastre et al, 2009) in an MDCK cell line that significantly over expresses MRP2 (Evers et al, 1998). This data is in general agreement with previous studies demonstrating that TxRd is a substrate of MRP2 (Leader and O'Donnell, 2005; O'Donnell and Leader, 2006). …”

Section: Discussionsupporting

confidence: 93%

Quantitative fluorescence microscopy provides high resolution imaging of passive diffusion and P-gp mediated efflux at the in vivo blood–brain barrier

Mittapalli

Manda

Bohn

et al. 2013

Journal of Neuroscience Methods

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Quantitative fluorescent microscopy is an emerging technology that has provided significant insight into cellular dye accumulation, organelle function, and tissue physiology. However, historically dyes have only been used to qualitatively or semi-quantitatively (fold change) determine changes in blood–brain barrier (BBB) integrity. Herein, we present a novel method to calculate the blood to brain transfer rates of the dyes rhodamine 123 and Texas red across the in situ BBB. We observed that rhodamine 123 is subject to p-glycoprotein mediated efflux at the rat BBB and can be increased nearly 20-fold with p-glycoprotein inhibition. However, Texas Red appears to not be subject to MRP2 mediated efflux at the rat BBB, agreeing with literature reports suggesting MRP2 may lack functionality at the normal rat BBB. Lastly, we present data demonstrating that once dyes have crossed the BBB, diffusion of the dye molecule is not as instantaneous as has been previously suggested. We propose that future work can now be completed to (1) match BBB transfer coefficients to interstitial diffusion constants and (2) use dyes with specific affinities to cellular organelles or that have specific properties (e.g., subject to efflux transporters) to more fully understand BBB physiology.

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Section: Discussionsupporting

confidence: 93%

Quantitative fluorescence microscopy provides high resolution imaging of passive diffusion and P-gp mediated efflux at the in vivo blood–brain barrier

Mittapalli

Manda

Bohn

et al. 2013

Journal of Neuroscience Methods

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“…Both OA and TA appear to modulate locomotor activity in the larva [65], [66] and in the adult fly [67], [68]. TA signaling also seems to influence diuresis [69]–[71] and olfactory behavior [72].…”

Section: Resultsmentioning

confidence: 99%

Neuroarchitecture of Aminergic Systems in the Larval Ventral Ganglion of Drosophila melanogaster

et al. 2008

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Biogenic amines are important signaling molecules in the central nervous system of both vertebrates and invertebrates. In the fruit fly Drosophila melanogaster, biogenic amines take part in the regulation of various vital physiological processes such as feeding, learning/memory, locomotion, sexual behavior, and sleep/arousal. Consequently, several morphological studies have analyzed the distribution of aminergic neurons in the CNS. Previous descriptions, however, did not determine the exact spatial location of aminergic neurite arborizations within the neuropil. The release sites and pre-/postsynaptic compartments of aminergic neurons also remained largely unidentified. We here used gal4-driven marker gene expression and immunocytochemistry to map presumed serotonergic (5-HT), dopaminergic, and tyraminergic/octopaminergic neurons in the thoracic and abdominal neuromeres of the Drosophila larval ventral ganglion relying on Fasciclin2-immunoreactive tracts as three-dimensional landmarks. With tyrosine hydroxylase- (TH) or tyrosine decarboxylase 2 (TDC2)-specific gal4-drivers, we also analyzed the distribution of ectopically expressed neuronal compartment markers in presumptive dopaminergic TH and tyraminergic/octopaminergic TDC2 neurons, respectively. Our results suggest that thoracic and abdominal 5-HT and TH neurons are exclusively interneurons whereas most TDC2 neurons are efferent. 5-HT and TH neurons are ideally positioned to integrate sensory information and to modulate neuronal transmission within the ventral ganglion, while most TDC2 neurons appear to act peripherally. In contrast to 5-HT neurons, TH and TDC2 neurons each comprise morphologically different neuron subsets with separated in- and output compartments in specific neuropil regions. The three-dimensional mapping of aminergic neurons now facilitates the identification of neuronal network contacts and co-localized signaling molecules, as exemplified for DOPA decarboxylase-synthesizing neurons that co-express crustacean cardioactive peptide and myoinhibiting peptides.

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“…Significant increases in transepithelial flux are seen only when the dye is present at concentrations close to or greater than the Michaelis-Menten parameter K t (O'Donnell and Leader, 2006). Regression analysis indicates that 57%-88% of the change in Texas Red flux can be attributed to the change in fluid secretion rate.…”

Section: Effects Of Fluid Secretion Rate On the Transport Of Organic mentioning

confidence: 99%

Too much of a good thing: how insects cope with excess ions or toxins in the diet

O’Donnell

2009

Journal of Experimental Biology

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SummaryMuch of our understanding of the ionoregulatory and excretory physiology of blood-feeding insects can be traced to a series of papers by Simon Maddrell and colleagues in the 1970s and 1980s. These studies of the Malpighian (renal) tubules of Rhodnius prolixus revealed a number of physiological adaptations to the short-term and long-term stresses associated with blood feeding. More recent electrophysiological studies using voltage-and ion-selective microelectrodes have extended our understanding of the mechanisms and control of ion transport by the secretory and reabsorptive segments of the Rhodnius Malpighian tubule. The discovery that the rates of transport of organic anions, urates and Ca 2+ are synchronized to coincide with the appearance of the products of blood meal digestion in the haemolymph of Rhodnius has stimulated parallel studies in Drosophila. This recent research has examined how excretory mechanisms for organic cations and organic anions are altered by exposure to such compounds in the diet. These studies also show that the Drosophila Malpighian tubule provides a useful model for analysis of the roles of transporters such as P-glycoproteins and multidrug resistance-associated proteins in the excretion of toxins.

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Changes in fluid secretion rate alter net transepithelial transport of MRP2 and P‐glycoprotein substrates in Malpighian tubules of Drosophila melanogaster

Cited by 17 publications

References 23 publications

Quantitative fluorescence microscopy provides high resolution imaging of passive diffusion and P-gp mediated efflux at the in vivo blood–brain barrier

Quantitative fluorescence microscopy provides high resolution imaging of passive diffusion and P-gp mediated efflux at the in vivo blood–brain barrier

Neuroarchitecture of Aminergic Systems in the Larval Ventral Ganglion of Drosophila melanogaster

Too much of a good thing: how insects cope with excess ions or toxins in the diet

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